TW201002728A - Heterocyclic urea derivatives and methods of use thereof - Google Patents

Abstract

Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

Description

201002728 VI. Description of the Invention: [Technical Field] The present invention relates to a compound exhibiting antibacterial activity, a process for preparing the same, and a pharmaceutical composition containing the same as an active ingredient, relating to its use as a drug and its use in manufacture Use in the treatment of a drug such as a bacterial infection of a warm-blooded human. In particular, the present invention relates to compounds suitable for the treatment of bacterial infections in warm-blooded animals such as humans, and more particularly to the manufacture of such compounds for the treatment of bacterial sensation in warm-blooded animals such as humans. [Prior Art] The international microbiological community has consistently expressed a strong emphasis on the fact that the evolution of antibiotic resistance can produce strains that are currently ineffective against bacterial agents. In general, bacterial pathogens can be used. It is classified as a Gram-positive or Gram-negative pathogen. Antibiotic compounds having an effective activity against both Gram-positive pathogens and Gram-negative pathogens are generally considered to have broad-spectrum activity. The compound is effective against Gram-positive pathogens and certain Gram-negative pathogens. Gram-positive pathogens (eg, Staphylococcus (SVap/^/ococcz·), Enterococci (Awierococci), Streptococcus, and Branches Bacilli are particularly important because they are difficult to handle once they are produced and are difficult to break away from the hospital environment. Sexual strains. Examples of such strains are methicillin-resistant Staphylococcus aureus (methicillin resistant less/ococcw·? awrew«s) (MRSA), anti-dioxobenzoic acid-induced coagulation 140628.doc 201002728 Enzyme-negative staphylococci (MRCNS), anti-penicillin-resistant pneumococci (penicillin resistant ("6), and multiple resistant protococci (multiple resistant five "ierococcwj /aec/· please") for these resistant Gram The preferred clinically effective vitamin for the last treatment of positive pathogens is vanco() myein. Vancomycin is a peptide and is associated with various toxicities including nephrotoxicity. Moreover, and most importantly, Anti-bacterial resistance to vancomycin and other glycopeptides occurs. This resistance is increased at a steady rate, making these agents less effective in treating Gram-positive pathogens. For the treatment of upper respiratory tract infections (which are also caused by certain Gram-negative strains, including Haemophilus influenzae (//···/(10) ζ) and Moraxella catarrhalis), Phenanone and macro ring Increasing resistance of esters. Therefore, in order to overcome the threat of a wide range of multi-drug resistant organisms, Dali needs to develop new antibiotics, especially with novel mechanisms of action and/or with new pharmacophoric groups. Antibiotics. Deoxyribonucleic acid (DNA) gyrase is a member of the π-type topoisomerase family that controls the topological state of DNA in cells (Champ〇ux,:

Ann· Rev· Biochem. 70: 369_413). The π-type topoisomerase uses the free energy derived from the hydrolysis of adenosine triphosphate (ΑΤΡ) to change the topology of the DNA by introducing an instantaneous double-strand break in the dna, passing the catalytic chain through the break and resealing the DNA. DNA gyrase is an essential and conserved enzyme in bacteria and is unique among topoisomerases in its ability to introduce a negative supercoil into DNA. The enzyme consists of two subunits encoded by phantom; rA and phantom; rB to form an A2:B2 tetrameric complex. The g-A unit of gyrase (GyrA) involves 140628.doc 201002728 in DNA fragmentation and resealing and contains a conserved (tetra) acid residue that forms a temporary covalent linkage to DNA during chain passage. The unit (GyrB) catalyzes the hydrolysis of ATP and interacts with the A-subunit to convert the free energy from hydrolysis into a conformational change in the enzyme that is capable of achieving chain passage and DNA resealing. Bacteria make another conserved and necessary π-type topoisomerase, which is called a topoisomerase, to be responsible for the separation of the linked closed circular bacterial chromosomes produced in replication. This enzyme is closely related to the DNA gyrase and has a similar tetrameric structure formed from a human unit homologous to GyrA and yrB. The overall sequence between the gyrase and topoisomerase IV is high in different bacterial species. Therefore, the compound with the bacterial type II topoisomerase has the potential to inhibit two targets in the cell (DNA gyrase and topoisomerase IV); the existing quinolone antibacterial agent is also the same (Maxwell, A_1997, ~ oil) Test _〇1· 乂102-109). DNA gyrase is a well-established target for antibacterial agents including quinolones and coumarins. Quinolone (eg, ciprofloxacin (cipr〇fl〇xacin)) is a broad-spectrum antibacterial agent (Drlica, κ and χ zha) that inhibits DNA cleavage and recombination of enzymes and captures GyA-human units covalently complexed with DNA. 〇, ι997, bi bi biol. Molec· Bi〇i. Rev· ό1: 377_392). Members of such antibacterial agents also inhibit topoisomerase IV and, therefore, the primary targets of such compounds vary from species to species. Although quinolones are successful antibacterial agents, resistance resulting from mutations in the target (DNA gyrase and topoisomerase IV) is a problem in several organisms including Staphylococcus aureus and Streptococcus pneumoniae. (Hooper, D_C_, 2002, The Lancet Infecti〇us D1Seases 2: 530_538). In addition, quinolone as a chemical produces toxicities 140628.doc 201002728 side effects, including its prevention of joint disease in children (Lipsky, BA and Baker, C. A. 1999, Clin. Infect. Dis. 28: 352-364). In addition, it may be predicted that cardiotoxicity has been proposed as a toxicity problem associated with quinolones as predicted by QTC interval prolongation. There are several known natural product DNA gyrase inhibitors that compete with ATP for binding to GyrB subunits (Maxwell, A. and Russell is a natural product isolated from the genus Spp. Chl〇robiocin and coumarinmycin A1). Although these compounds are potent DNA gyrase inhibitors, they are toxic due to their toxicity in eukaryotes and poor in Gram-negative fines. 'Therefore, its therapeutic utility is limited (Maxwell, A. 1 997, Trends Microbiol. 5: 102-109). Another natural product class that targets GyrB subunits is cycloCi〇thiali (iine). ), which is from the Philippines Isolation of mold (twisting (10) less (10) force 7 such as Lai·s) (Watanabe, j et al., 1994, J. 47: 32-36). Although effective against the spirulina, the cyclothiazide is still A poor antibacterial agent that exhibits activity only for some eubacterial species (Nakada, N, 1993, YANG. C/ze/woi/zer. 37: 2656-2661) ° Targeting DNA gyrase is known in the art And a synthetic inhibitor of the topoisomerase in B units. For example, the coumarin-containing compound is described in the patent application No. WO 99/35 155, in the patent application WO 02/060879 The 5,6-bicyclic heteroaromatic compound is described, and the pyrazole compound is described in the patent application WO 01/52845 (U.S. Patent No. 6,608,087). 140628.doc 201002728

AstraZeneca has also disclosed certain applications for the description of antibacterial compounds: WO 2005/026149 > WO 2006/087544, WO 2006/087548, WO 2006/087543 'WO 2006/092599, WO 2006/092608 and WO 2007/071965. SUMMARY OF THE INVENTION We have discovered a new class of compounds suitable for inhibiting DNA gyrase and/or topoisomerase IV. In one embodiment, according to the present invention, there is provided a compound of formula (I):

Or a pharmaceutically acceptable salt thereof, wherein: X is N, CH or CR4; [alkyl group, -CH^CH-CCw alkyl group) or -C3 CHCu alkyl group), wherein When L is -CH^CH^Cwalkyl) or -C^C^C!·4alkyl), the double bond or the bond is the point of attachment to the ring A; R1 is selected from C!_6 alkyl a C2_6 alkenyl group, a C2.6 alkynyl group or a C3.6 cycloalkyl group; wherein R1 is optionally substituted on the carbon by one or more R7; R2 is selected from hydrogen or C!-6 alkyl; wherein the Cw alkyl group Optionally, substituted by one or more groups independently selected from halo, cyano, hydroxy, nitro and amine; or R1舆R2 together with the nitrogen to which they are attached form a heterocyclic group; wherein the hetero 140628. Doc 201002728 D is substituted by one or more R 8 on one or more carbon atoms; and eight: 4 heterozygous contains a =N or _s_ moiety, then the nitrogen may optionally be via a pendant oxy group. Substituting and the sulfur may be substituted by - or two pendant oxy groups; and the octagonal group contains the ._ moiety, the gas may be substituted by a group selected from r9; R is hydrogen 'C, _6 Alkyl, (Ci 6 alkyl) 3 decyl, c3 carbocyclyl or "in the middle of r3" Substituting one or more substituents on - or a plurality of carbon atoms and wherein if the heterocyclic group contains a =N- or -S- moiety, the gas may optionally be via a gamma fj wing % & nu 1 Substituted and sulfonium thiophene may be substituted by one or two pendant oxy groups, and wherein if the heterocyclic group contains a ΝΗ moiety, the nitrogen may optionally be substituted with a group selected from R11; Independently selected from the group consisting of cumyl, nitrogen, trans, amine, sulfhydryl, Cw alkyl, c2-6 dilute C2-6, Ci 6 alkoxy, ( Ci-6-formyl) amine n (CK, tertino) 2 amine group and CN6 alkylthio group; wherein each occurrence of r4 independently depends on one or more R12 on the moon or on the carbon atom Substituted; is hydrogen or a hetero group, wherein the heterocyclic group may optionally be substituted on one or more carbon 1 groups, =S or one or more R14; and wherein if the heterocyclic group 3 has N & S-彳分', the nitrogen may be optionally substituted by a pendant oxy group and the sulphur may be optionally substituted with - or two pendant oxy groups; and wherein if the heterocyclic group 3 has -NH-. Nitrogen can be selected from r 〖7 Substituted by a group; when R is present, the group is independently selected from the group consisting of the following groups: a group of a nitro group, a thiol group, an amine group, a sulfhydryl group, an amine group, an anthracene, a s Ci- 6 alkyl, c2.6 alkenyl, c26 alkynyl, Ci 6 alkoxy, 140628.doc 201002728 alkyl) amine, MAKCu alkyl h-amine, Cl_6 alkyl s(〇)a_ (where & Anthracene, 1 or 2), alkyl)aminesulfonyl, m^(Ci_6 alkyl)2aminesulfonyl, alkylsulfonylamino, carbocyclyl and heterocyclic; Independently, depending on the case, substituted by one or more • R on one or more carbon atoms, and wherein if the heterocyclic group contains a =N- or -S- moiety, the nitrogen may optionally be via a pendant oxy group. Substituted and the sulfur may be optionally substituted with or with two pendant oxy groups; and wherein if the heterocyclic group contains a _NH_ moiety, the nitrogen may optionally be substituted with a group selected from R13; f^...m is 〇 or 1 ; p is 0, 1, 2 or 3; the ring B is a C3_M carbocyclic group or a heterocyclic group; wherein if the heterocyclic group contains a _nh_ moiety, the nitrogen may optionally be substituted with a group selected from the group; If the heterocyclic group contains a =N- or -S- moiety, the nitrogen Substituted by a pendant oxy group and optionally substituted by one or two pendant oxy groups; R, R, R, R12, ^^ and 尺^ are substituents on carbon, each of which is currently independent Selected from: _ base, ruthenyl, cyano, thiol, amine, benzyl, amine carbhydryl, thiol, amine thiol, Ci 6 alkyl, & dilute, Cw alkynyl, Cl_6 Alkoxy group, Cl. 6 alkyl alkanoyl group, Ci 6 alkyl fluorenyloxy group, pyro-(C 6 · 6 alkyl) amine group, π 沁 (Cw alkyl) 2 amine group, d 6 alkyl amidino group, - Alkyl)amine carbaryl, hydrazine (c) _0 alkyl) 2 amine carbhydryl, alkyl S (〇) a_ (where 3 is ruthenium, u2), Ci6 aerobic group, c "6 burnt Oxygen-based group, oxime (C -6 alkyl) aminoxime, ruthenium (c) _6 alkyl) 2 amine sulfonyl, Cyalkyl sulfonylamino, _L2_C3 · 6 carbon ring Or a 彳2_heterocyclic group; wherein RR, 尺, R, r14ir, 6 are independently of one another, or may be substituted by one or more than one R, 60628.d〇 (201002728 multiple carbons; or The heterocyclic group contains a -JNM- moiety, and the lean & , , ^ αΛ虱 may be optionally substituted with a group selected from the group consisting of r2Q; And wherein if the heterocyclic group contains =~..^, or ·S_#, the nitrogen may be replaced by a 5 soil: and the sulfur may be substituted by - or two pendant oxy groups; direct bond, - 〇·, _N(R18), , -C(0)N(R'8). . ern, c , 18—(〇)P-, _S〇2N(R18)- or -N(R18)S〇2 - wherein R = sub-occurrence is independently hydrogen or Cl. 4 alkyl and P is 0-2; R, 1115, 1^17 and 112 are each independently selected from the group consisting of decyl C3_6 alkane Base, Ci_6 alkyl fluorenyl, Ci_6 alkyl sulfonyl, Ci6 alkoxy methoxy, amine carbhydryl, alkyl) amine carbhydryl, ruthenium (Cl_6 alkyl) amine methyl thiol, benzyl, benzene a methoxycarbonyl group, a methionyl group and a phenyl K fluorenyl group, wherein R9, RU, R13, R15, R17 and R20 are independently substituted with one or more R23 on the carbon, respectively; and each of R19 and R23 is present. The time is independently selected from the group consisting of halo, nitro, cyano, hydroxy, difluoromethoxy, trifluoromethyl, amine, carboxyl, amine fluorenyl, fluorenyl, sulfonyl, methyl, ethyl , methoxy, ethoxy, ethoxylated, ethoxylated, methylamino, ethylamino, dimethylamino, diethylamine , mercapto-iV-ethylamino, etidinyl, methylamine, mercapto, ethylamine fluorenyl 'W-didecylamine decyl, jv, iv-diethylamine Base, methyl-hydrazine-ethylamine methyl sulfhydryl, sulfonylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, fluorenylcarbonyl , ethoxycarbonyl, iV-decylamine sulfonyl, ethylamine sulfonyl, dimethylamine sulfonyl, 7V, iV-diethylamine sulfonyl or V-methyl-7V-B Amidoxime. 140628.doc •10· 201002728 In another embodiment, the invention provides a medicament comprising a compound represented by formula (i) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier combination. In another embodiment, the invention provides a method of inhibiting bacterial DNA gyrase and/or bacterial topoisomerase IV of a warm-blooded animal in need thereof, comprising administering to the animal an effective amount of formula (I) A compound represented by the use thereof or a pharmaceutically acceptable salt thereof. In a particular embodiment, the warm-blooded animal is human. In another embodiment, the invention provides a method of producing an antibacterial effect in a warm-blooded animal in need of treatment, comprising administering to the animal an effective amount of a compound represented by formula (I) or a pharmaceutically acceptable compound thereof Accept the salt. In a particular embodiment, the warm-blooded animal is a human. In another embodiment, the invention provides a method of treating a bacterial infection in a warm-blooded animal in need thereof, comprising administering to the animal an effective amount of a compound represented by formula (I) or a pharmaceutically acceptable compound thereof salt. In a particular embodiment, the warm-blooded animal is a human. In one embodiment, the bacterial infection is selected from the group consisting of: community-type infection pneumonia, hospital-type infection pneumonia, skin and skin structure infection, acute exacerbation of chronic bronchitis, acute sinusitis, acute otitis media, catheter Related sepsis, febrile neutropenia, osteomyelitis, endocarditis, urinary tract infections, and infections caused by drug-resistant bacteria, such as Streptococcus pneumoniae, anti-Bencillin Staphylococcus aureus, Staphylococcus aureus resistant to methicillin (methicillin-resistant e/jz'i/erw/c/b) and vancomycin against vancomycin. In a particular embodiment 140628.doc -11 - 201002728, the warm-blooded animal is a human. In another embodiment, the present invention provides the use of a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for producing an antibacterial action in a warm-blooded animal. In a particular embodiment, the warm animal is a human. In another embodiment, the present invention provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a bacterial DNA gyrase and/or topoisomerase IV for use in inhibiting warm-blooded animals. The use of the drug. In a particular embodiment, the warm-blooded animal is a human. In another embodiment, the present invention provides the use of a compound represented by formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of bacterial infection in a warm-blooded animal. In one embodiment, the bacterial infection is selected from the group consisting of: community-type pneumonia, hospital-type infection pneumonia, skin and skin structure infections, acute exacerbation of chronic bronchitis, acute sinusitis, acute otitis media, catheter-related Sepsis, febrile neutropenia, osteomyelitis, endocarditis, urinary tract infection, Streptococcus pneumoniae resistant to penicillin, Staphylococcus aureus resistant to methicillin, methicillin resistant Staphylococcus epidermidis and vancomycin resistant to vancomycin. In a particular embodiment, the warm-blooded animal is a human. In another embodiment, the present invention provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof for producing an antibacterial action in a warm-blooded animal. In another embodiment, the present invention provides a compound represented by formula (I) for inhibiting bacterial DNA gyrase and/or topoisomerase IV of a warm-blooded animal, 140628.doc -12-201002728 or a medicament thereof A salt that is acceptable for learning. In another embodiment, the present invention provides a compound represented by formula (1) or a pharmaceutically acceptable salt thereof for use in the treatment of a warm-blooded animal. - In another embodiment, the present invention provides a compound for treating the following: a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof: a community-type infection, a fire, a hospital-type infection pneumonia, a skin and Skin structure infection, acute exacerbation of chronic branch 1 ex, acute sinusitis, acute otitis media, catheter-related i sepsis, febrile neutropenia, osteomyelitis, endocarditis, urinary tract infection, anti-panicillin Streptococcus pneumoniae, Staphylococcus aureus against phthalocyanine, Staphylococcus epidermidis resistant to methicillin or Enterococcus faecalis resistant to Vancomycin. [Embodiment] In the present specification, the term filament includes a linear and branched saturated hydrocarbon group. By way of example, 5' "cN6 alkyl" means a alkyl group having from 1 to 6 carbon atoms and includes, for example, methyl, ethyl, propyl, isopropyl and t-butyl groups. However, unless otherwise specified (e.g., propyl), reference to an individual alkyl group (such as propyl) is specifically meant to be a straight-chain version. Similar conventions apply to other general terms. Unless otherwise specified, otherwise the alkyl group may be the same when represented by, for example, the term I alkyl) 2 (such as in the term • AM(Cl 6 alkyl) 2 amine group), two or more alkyl groups. Or different. As used herein, the term "extension" refers to a divalent alkyl group linking two other groups. "C1.6 Stretching base" means an extensor having (1) carbon atoms. An example of an alkylene group is a methylene group. 140628.doc -13- 201002728 As used herein, the term "olefin" refers to a straight or branched chain hydrocarbon having one or more double bonds. Examples of the olefin include a vinyl group, a 3-butyl group, and the like. The term "alkenyl group" as used herein refers to a divalent alkenyl group linking two other groups. "Cw-extended alkenyl" means an alkenyl group having 1 to 6 carbon atoms. Examples of alkenyl groups include -CH=CH-, _(^2(:Ι·Ι=CHCH2- and the like. As used herein, the term "alkynyl" refers to having one or more referenced bonds. Straight or branched chain hydrocarbons. Examples of alkynyl groups include ethynyl, 3-propyl-c-indene and the like. The term 'extensional alkynyl' as used herein refers to the divalent linking of two other groups. Alkynyl. "Cl_6 "alkynyl" means an alkynyl group having 1 to 6 carbon atoms. Examples of an alkynyl group include _CHsCH_, _eH2eH = chch2- and the like. The term r Ci_6 as used herein. "Haloalkyl" means an alkyl group having from 1 to 6 carbon atoms in which one or more of the carbon atoms is substituted with a mercapto group. Representative alkyl groups include _CF3, _CHF2, _ccl3, _CH2CH2Bp. ΗΐαΗ3& is a similar group. As used herein, the term 'dentate group' refers to a fluoro group, a chloro group, a molybdenum group and a fluorenyl group. The:heterocyclic group has 4 to 14 atoms, wherein at least one of the atoms is selected from a saturated, partially saturated or unsaturated monocyclic or bicyclic ring of nitrogen, sulfur or oxygen, which may be a ruthenium or a nitrogen bond, except _ch2- Alternatively, m -c(〇)-substitution' and the ring sulfur atom may be oxidized as appropriate to form an s_oxide. In the present invention, the "heterocyclic group" contains 5 or 6 atoms, and (d) at least one atom Is selected from the saturation of nitrogen, sulfur or oxygen, 140628.doc -14-201002728 is a saturated or unsaturated monocyclic ring, unless it is given PXJ I, brother Ming 'otherwise it can be carbon or nitrogen linkage, -CHr group It may be replaced by _α, i „(〇)-, and the ring sulfur atom may be oxidized as needed to form an S-oxide. In another aspect of the invention, the "hetero-base" contains 5 or 6 One atom, complex φ. ^ at least one atom selected from nitrogen, squash or oxygen is unsaturated with carbon bonded sir, "early %. In another aspect of the invention, 'heterocyclic group" is not Saturated and closed | _ 夂 基 group. The term "heterocyclic group" and the appropriate meaning are morpholinyl, earth, D than bite base, U base base, mouth than Loki, sit Base, iso-salt, aryl, fluorenyl, fluorenyl, 1'3_open dioxapentenyl, material (tetra)yl sylylene, oxadiyl, piperazinyl, Zyridinyl, > pyridine, thiomorpholinyl, pyrrolinyl, levothazine, 3,5-dioxa, & glycan, tetrahydropyranyl, imidazole , 4,5-dihydro-oxazolyl, oxime, 0-azinyl, pyridazinyl, isoxazolyl, thiazolyl, 1//-tetrazolyl, 1/7_-- iV-mercaptopyrrolyl, 4_ fluorene, quinone, quinoline _4 (1//) ketone, pyridinium?) 疋-to 1 tablet), ketone, imidazo[l,2-a] pyridine Isoindanones, 2H ketones, butyl phthalocyanine, 5'6 dihydro (10) (tetra) and (10) oxazinyl, _j oxides and cerium oxides. A suitable example of the "nitrogen-bonded heterocyclic group" is n. morpholinyl: piperazin-1-yl, piperidine "base and imidazole". In another aspect of the invention, the "heterocyclyl" is an unsaturated and aromatic group. Examples and suitable meanings of the aromatic heterocyclic ring include pyridyl, pyrrolyl, pyrazolyl, isothiazolyl. Introducing scent base, sputum base. Queenyl, benzoindol, di-salt, s-saltyl H, (d), Dtt ^methyl, benzyl, carbazyl, thiazolyl, 1//tetrazole, 17 /_Triazolyl, fluorenylmethyl fluorenyl, quinoline-4(10))··, pyridine 2〇//) ketone, imidazolium oxime ratio pyridine group, 1 ^ 140628.doc •15- 201002728 啥诺_, $ spider base'. Than ^_ oxide and 嗤 I I oxide. "Carbocyclyl" is a saturated, partially saturated or unsaturated monocyclic, bicyclic or tricyclic carbocyclic ring containing from 3 to 14 atoms; wherein the - group may be optionally substituted by -C(〇)-. In the "shooting", the "carbocyclic group" is an early soil containing W atoms or a double ring containing 9 or 1 atom. Examples of the carbocyclic group include a cyclopropyl group, a cyclobutyl group, a pendant oxycyclopentyl group, a cyclopentyl group, a cyclopentenyl group, a cyclohexyl group, a cyclohexenyl group, a phenyl group, a naphthyl group, a tetralinyl group, and a second group. Hydrogen nodal or 1_oxydihydrogenation. The term carbocyclyl encompasses both cycloalkyl and aryl. In a particular embodiment, the carbocyclic ring is a 4-aryl group. The c(4)aryl group is an aromatic monocyclic, bicyclic or tricyclic carbocyclic ring containing 6 to 14 atoms. Examples of the aryl group include a phenyl group and a naphthyl group. As used herein, "(Cl_6 alkyl) 3 decyl" is a radical having three independently selected groups, such as trimethyl ketone and dimethyl-tert-butyl fluorenyl. An example of a C,-6 alkyl alkoxy group is an ethoxy group. Examples of the "c" alkoxycarbonyl group" are a methoxy group, an ethoxy group, a n-butoxy group and a third butoxy group. Examples of the "C1 oxiranylamino group" are an methoxymethylamino group, an ethoxymethylamino group, a n-butyl fluorenyl group, and a third butanoxy group e "c" alkoxy group. Methoxy, ethoxy and propoxy. Examples of "cl-6 decylamino" are carbamide, acetamino and propylamine. "C14-based S(〇)a (wherein Examples of 40, w)" are methylthio, ethylthio, methyl sulfenyl, ethyl fluorenyl, fluorenyl and ethyl fluorenyl. "Example of Cw sputum" is C醯基和乙醯基。w Examples of "Fantasy Amino Group" are methylamino and ethylamino. "Heart (c"院基)2Amino" 140628.doc 16· 201002728 The example is di-ΛΓ- Methylamino, diethyl)amino and ethylmethylamino. Examples of "Cm alkenyl" are vinyl, allyl and anthracenyl groups. Examples of the "C2_4 fast radical" are ethynyl, fluorenyl-propynyl and 2-propynyl. Examples of "AKCw alkyl)amine sulfonyl are #_(methyl)amine sulfonyl and oxime (ethyl) sulfonate. Examples of "iV'iVJCi-6 alkyl)2aminesulfonyl" are #,#-(dimethyl)aminesulfonyl and #_(methyl)_#_(ethyl)aminesulfonyl. Examples of the "^_(C decyl)aminomethane group" are a τ-aminocarbonyl group and an ethylaminocarbonyl group. Examples of the "MAKC, · 6 alkyl) 2 amine carbenyl group are dimethylaminocarbonyl and decylethylaminocarbonyl. Examples of the "AT-(Cl.6 alkoxy)amine fluorenyl group" are a methoxyaminocarbonyl group and an isopropoxyaminocarbonyl group. Examples of "Hyperyl"-'(Cm alkoxy)amine hydrazino are methyl-methoxyaminocarbonyl and methyl-ethoxyethoxycarbonyl. Examples of the "C3·6 cycloalkyl group" are a cyclopropyl group, a cyclobutyl group, a cyclopropyl group and a cyclohexyl group. Examples of the "Ci6 alkylsulfonylamino group" are a mercapto-based mercaptoamine group, an isopropyl sulfhydrylamino group, and a tert-butylsulfonylamino group. Examples of the "C,6 alkylsulfonylaminocarbonyl group" are a methylsulfonylaminocarbonyl group, an isopropylsulfonylaminocarbonyl group, and a tert-butylsulfonylaminocarbonyl group. Examples of "C alkylsulfonyl" are methylsulfonyl, isopropylsulfonyl and tert-butylsulfonyl. Unless otherwise specified, the term "formula (1)" refers to all embodiments of formula (1), including but not limited to formula (ia), formula (11), and formula (Ic). The compound of formula (I) may form a stable acid or base salt, and in such cases it may be appropriate to administer the compound in the form of a salt, and may be made pharmaceutically acceptable by conventional methods such as those described below. Accept the salt. Suitable pharmaceutically acceptable salts include acid addition salts such as methyl sulphate 140628.doc -17- 201002728 acid salt, toluene acid salt, alpha glycerol acid salt, fumarate salt, hydrochloric acid Salt, citrate, maleate, tartrate and (secondary) hydrogen oxalate. Salts formed with phosphoric acid and sulfuric acid are also suitable. In another aspect, a suitable salt is an alkali salt such as a metal salt such as a sodium salt; a soil metal salt such as a phosphonium salt or a magnesium salt; an organic amine salt such as triethylamine, morphine, #_甲Basement 疋, Λ/"-ethyl 〇 》 定 、, procaine (pr〇caine), diphenyl decylamine, 沁 沁 苯 苯 、 参 参 参 参 ( ( ( 2 2 2 2 2 Amine, hydrazine methyl glucosamine and salts of amino acids such as lysine. Depending on the number of charged functional groups and the valence of the cation or anion, more than one cation or anion may be present. A preferred pharmaceutically acceptable salt is the sodium salt. However, to facilitate separation of the salt during preparation, salts which are less soluble in the solvent of choice may be preferred either pharmaceutically acceptable or pharmaceutically unacceptable. & In the present invention, it is to be understood that the compound of the formula (1) or a salt thereof exhibits a phenomenon of mutual mutation, and the chemical formula in the present specification may represent only one of the possible tautomeric forms. It will be understood that the invention encompasses inhibiting any tautomeric form of the capsular rotase or topoisomerase and is not limited to chemistry; any tautomeric form used in the scheme. The 4 schemas in this specification may only indicate possible interconversions..., "One of the mutual k-isomeric forms and should be understood, the book covers the compounds drawn, and not only has been possible in this paper ^ Tautomeric forms of gates are shown in graphical form. The same applies to the compound name. ~# Those skilled in the art should be aware of the carbon and/or sulfur atoms of a certain generation, and:: The compound of formula (1) contains no loss and therefore can be optically active and racemic 3 140628.doc 18 201002728 exists, It is optically active and racemic, and it is separated from the knife. Some compounds can show polymorphism. It is to be understood that the present invention encompasses any of the racemic, optically active isomeric forms or mixtures thereof, which have properties suitable for inhibiting DNA gyrase and/or topological, denier 1 ν, in which How to prepare an optically active form (for example, by recrystallization to resolve a racemic form, by synthesis from an optically active starting material, by: sexual synthesis, by enzymatic resolution, by biotransformation or by the use of palmarity) The stationary phase is chromatographed) and how it is effected by the following standard DNA gyrase and/or topoisomerase.疋 疋 Inhibition For clarity, the compounds of the present invention include all isotopes present in formula (1) and any of the examples or examples disclosed herein. For example, a ' Η (or 虱) means any hydrogen of the same 3Hm. Γ# _ . 7, "formal form, including *H, 2H (9) and

Hm, / any isotopic form of the form includes ^, % and "C; 〇 means any isotopic form of oxygen, including 16 〇, , f: isotope form, including,,, and, two:: Isotopic forms, including 31p and 32, including 32S and "SF" ~ any isotopic form

.18ρ . Γ| , any isotopic form not rolled, including 同9F and ^ any non-chlorinated isotope 36Γ1. Fengan^ 位 morphin form, including 35C1, 37C丨 and the like. In the preferred embodiment, the compound represented by the formula (1) contains an isomer in which an atom is present, and in some cases, an isomer is required. However, it is necessary to make - or a plurality of atoms rich in specific isotopes that would normally exist in the same degree. For example, 99.98% Feng Tang is in the strength of Miao Er, and the compound of the present invention is rich in multiple times in the position of H. In the specific example of the compound of formula (1) 140628.doc -19- 201002728 'When, for example, hydrogen is rich in helium isotope, the symbol "D" is used to indicate the richness of the plant. In one embodiment, when the compound of the invention is rich in radioisotope isotopes (for example, 3H and 14c), the cockroach can recognize the „, and the τ can be applied to the music and/or the substrate. It is understood that the present invention encompasses all such isotopic forms that inhibit DNA gyrase and 7-peptase IV. It is also understood that certain compounds of formula (1) and salts thereof may be solvated as well as unsolvated forms. (such as a hydrated form) is present. It is to be understood that the invention encompasses all such solvated forms which inhibit DNA gyrase and/or topoisomerase! v. Certain substituents and groups mentioned herein are mentioned herein. Specific and appropriate meanings. Where appropriate, such meanings may be used in any of the definitions and embodiments disclosed above or below. aa * For the avoidance of doubt, the various substances represent specific and independent aspects of the invention. In one embodiment, the invention provides a compound represented by formula (1) wherein X is CH. In another embodiment, the invention provides a compound represented by formula (1) wherein X is N. In another embodiment The invention provides A compound represented by the formula (1), wherein X is CR4 and R4 is a fluoro group, a chloro group, a bromo group, an iodo group, a Ci*alkyl group or a Cm alkoxy group. In another embodiment, the present invention provides a formula ( 1) A compound represented by wherein L is a CM alkynyl group, for example _CsC_. In a particular embodiment, [is -C = C-(C!.4). In another embodiment, The invention provides a compound represented by the formula (1), wherein L is a C2·6-extended alkenyl group. In a specific embodiment, [is _(:11=(::11_((::1*140628.doc •20) - 201002728 alkylene). In another shell example, the present invention provides a compound represented by the formula (1), wherein L is (^-6 extended alkyl). In another embodiment, the present invention provides a formula (1) a compound wherein the oxime is a 5- or 6-membered heteroaryl group, and wherein if the heteroaryl group contains a leu- moiety oxime, the nitrogen may optionally be substituted with a group selected from Rl5; and wherein the heteroaryl group 3胄N· or -s·部分', the atmosphere may be optionally substituted by a pendant oxy group and the sulphur may be substituted by one or two pendant oxy groups. In another example, the invention provides a formula (1) Combination Or a sulfhydryl group, a pyridyl group or a thiazolyl group; and wherein each of the pyridyl group, the pyridazyl group, the timidyl group or the oxime group may be independently substituted with a side milyl group; And wherein each part of the oxime group may be optionally substituted with or with two pendant oxy groups. In another embodiment, the invention provides a compound represented by the formula (1), which is a bicyclic heterocyclic group; The ring group contains a _Simplified_ moiety, and the nitrogen may be optionally substituted with a group selected from Rl5; wherein the base contains an m moiety, the nitrogen may optionally be taken by a side oxy group: and the sulphur may be subjected to one or The two side oxy groups are substituted. In the two-(four) column, the present invention provides a compound represented by the formula (1), and the clothes thereof are exemplified.右琳基 or 5,6_Dihydro π,3]嗟 并 and [4,5, oxazine and wherein 5,6· dihydroanthracene, 3 mers [4,5•朴秦句_二^ Η- Partially, independently, may be substituted by a group selected from R.5. The intermediate group or M-dihydrofl, and [4,5♦dazine'7_2: each N- independently Substituted by a pendant oxy group; and wherein

, ^ I I40628.doc 21 201002728 虱Π, 3] thiazolo[4,5_4哒唪奈, the -S- moiety of 7-one ketone may optionally be substituted by one or two pendant oxy groups. In the examples, the present invention provides a compound represented by the formula (1), wherein the anthracene ring is. Ratio π is fixed; and wherein = - is replaced by a pendant oxy group according to the condition. In one embodiment, the anthracene ring is an unsubstituted pyridyl group. In the embodiment, the present invention provides a compound of the formula ((10) wherein the anthracene ring is a C3_M carbocyclic group, such as a phenyl group. In another embodiment, the invention provides a compound represented by the formula (1) wherein R is c , -6 alkyl. For example, R1 is methyl, ethyl, propyl, propyl 'butyl, isobutyl, second bismuth. In a particular embodiment, R1 is ethyl. Its hetero-M- In another embodiment, the present invention provides that the compound represented by the formula (1) wherein R is hydrogen. In the embodiment, the present invention provides a compound represented by the formula (1) wherein R is <^__6 alkyl. For example, Han 2 is soil C* lane, propylpropyl, butyl 'isobutyl, second butyl and tert-butyl. In another embodiment - The invention provides that R3 of the compound represented by the formula (1) is a 5-membered heteroaryl group; and wherein the heteroaryl group may be optionally substituted with one or more R1 groups on one or more carbon atoms; and wherein if or -s- In part, the nitrogen may be substituted by _ 3 - N_ ^ Ό U-milk base and the sulfur may be substituted with two pendant oxy groups; and wherein if the (tetra) aryl group - NH- moiety, the nitrogen may be used as the case may be.杳# n At < group substitution. In one aspect of this example, R, ° is selected from the group consisting of methyl, phenyl, trifluoromethyl, and pyridyl. In this embodiment In another embodiment, the present invention provides a compound represented by the formula (1), wherein R 3 is a thiazolyl group; and wherein the thiazolyl group is optionally in the carbon Substituted by one or more R1G; and wherein the thiazolyl group = N_ may be substituted by a side oxy group 'and /, the snail group may be substituted by one or two side thiol groups. In one aspect of the invention, R10 is selected from the group consisting of methyl, phenyl, trifluoromethyl and pyridyl. In another aspect of this embodiment, R11 is fluorenyl.

In another embodiment, the present invention provides a compound represented by the formula (1), wherein R3 is I,3'4-oxadiazolyl; and wherein the ^4·oxadiazolyl group may optionally be on one or more carbons Substituted by one or more Ri(R); and wherein each of the U3,4-oxadiazolyl groups = N_ can be independently substituted with one pendant oxy group as appropriate. In this embodiment, the sample is selected from the group consisting of methyl, phenyl, and trimethyl. A group consisting of pyridine groups. In another aspect of this embodiment, R11 is a fluorenyl group. In another embodiment of the present invention, the present invention provides a compound represented by the formula (1), wherein R is 1 //-pyrazolyl; and wherein the n-azozolyl is optionally present in one or more than one slave R1◦ is substituted; and wherein the pyrazole group=N_ can be optionally substituted with one pendant oxy group; and wherein the 1/7-pyrazolyl group is substituted with a group selected from RU. In one aspect of this embodiment, R1. One is selected from the group consisting of methyl, phenyl, trifluoromethyl and pyridyl. In another aspect of this embodiment, R11 is methyl. In another embodiment, the present invention provides a compound represented by formula (I), wherein R is iota, 3- benzothiazolyl; and wherein the 1>-3-benzothiazolyl group is optionally present on or after the carbon Substituted by one or more R10; and wherein 丨, 3_笨和叹140628.doc -23- 201002728 σ sits on the base - N' can be replaced by a side oxy group; and wherein 1,3-benzopyrene Sit-based -S - visually - or substituted with two pendant oxy groups. In one aspect of this embodiment, the Ri(R) is selected from the group consisting of a fluorenyl group, a phenyl group, a trifluoromethyl group, and a pyridinyl group. In another aspect of this embodiment, r1! is a methyl group. In another embodiment, R3 is optionally substituted with one or more independently selected Ri(R) on one or more carbon atoms. In one embodiment, 'R3 is tridecyl. In a further target, r3 is a 6 alkyl group optionally substituted with one or more independently selected Rio on one or more carbon atoms. In one embodiment, R0 is independent each time it occurs. Is selected from the group consisting of C"alkoxy, _〇_C3 6 carbocyclic and hydrazine-heterocyclyl. In one embodiment, r3 is methoxymethyl. In another embodiment 'R3 is tetrahydro _ 2 / / _ piperidine 2 - fluorenyl. In another embodiment, the present invention provides a compound represented by the formula (1), wherein two are 4-fluoromethyl thiazol-2-yl, four specific pyridines 2_yl)thiazol-2-yl, 4-phenyl-嗟sa_2_, 彳q 1,3-open thiazole-2-yl, 2-(pyridine-4-yl)- 1,3 , 4-oxadiazole _5-yl, oxime methyl ^ 巧 _ base, ι_methyl-...pyrazol-4-yl, 2-methyl. Oxadiazol group or 4_(pyridine·-2-yl. In the examples, the present invention provides a compound represented by the formula (1):: a heteronym; and t=N- optionally substituted by a sideoxy group In a consistent embodiment, R3 is an unsubstituted fluorenyl group. In the present embodiment, 'the present invention provides a compound represented by the formula (1); '', as the case may be - or a plurality of carbon atoms through one or more Ri. Take, then 6-14 square. 140628.doc •24· 201002728

In another embodiment, the present invention provides a compound represented by the formula (1): wherein R 5 is a five-membered aromatic heterocyclic group, and wherein the heterocyclic group may optionally be on one or more carbon atoms - or a plurality of r 14 Substituting; and wherein if the heterocyclic group contains a =N- or _S. moiety, the nitrogen may optionally be substituted with an oxy group and the sulphur may be optionally substituted with - or two pendant oxy groups; The ring group contains a -NH- moiety, and the nitrogen may optionally be substituted with a group selected from r". In the aspect of this embodiment, the R" is selected from the group consisting of Ci 4 alkyl or via. In another aspect of this embodiment, R17 is a C1-4 alkyl group. In another embodiment, the invention provides a compound represented by formula (1), wherein R5 is selected from the group consisting of the following groups: : oxadiazolyl, 1,3,4-thiadiazolyl, 1/7-tetrazolyl, oxadiazolyl, pyrazolyl, 3/M, 2,3,5-oxathiadiazolyl,丨 - - imidazolyl, morpholinyl, 4,5-dihydro-oxazolyl and 1/-1,2,4-triazolyl, wherein the oxime 'oxadiazolyl, 1,3, 4. Thiadiazolyl, tetrazolyl 'oxadiazolyl, pyrazolyl, 3/Μ, 2, 3, 5 - oxathiadiazolyl, imidazolyl, morpholinyl, 4,5-dihydro-oxazolyl and 1/-1,2,4-triazolyl may optionally be on one or more carbon atoms Or a plurality of R14 substituted; and wherein hydrazine, 3,4-oxadiazolyl, 13, 'thiadiazolyl, 1/--tetrazolyl, 1,2,4-oxadiazolyl, pyrazolyl, 3 good _ 1,2,3,5-° evil '1 stopper a salivation, 1//-imilyl, 4,5_ dihydro-11 ox 11 sitting base and 1 open _ 1,2,4- The =N- moiety of the triazolyl group may be optionally substituted with one pendant oxy group and the _S_ moiety of the 1,3,4-thiadithiol or 3/M,2,3,5-oxathiadiazolyl group may be used as the case may be. Substituted by one or two pendant oxy groups; and wherein 1 dan-4-tetrazolyl, 1 danylpyrazolyl, 3//-1,2,3,5-oxathiadiazolyl, imidazolyl, morpholinyl Or the -NH- moiety of the 1,2,4-triazolyl group may be optionally substituted with a group selected from Ri7. 140628.doc 25- 201002728 In one of the examples B, R]4 is selected from the group consisting of Gy alkane A group consisting of a hydroxyl group or a hydroxyl group. In one embodiment of this embodiment, R17 is a CM alkyl group. In another embodiment, the present invention provides a compound represented by the formula (1), wherein R5 is a group represented by the following formula : * 〇, V〇

N-N Η where "*" indicates the connection point with the ankle ring. In another embodiment, the present invention provides a compound represented by the formula (1), wherein m is 0. In another embodiment, the present invention provides a compound represented by the formula (1), wherein m is 0 and X is CH. In another embodiment, the present invention provides a compound represented by the formula (1), wherein m is 0 and X is N. In another embodiment, the present invention provides a compound represented by the formula (1), wherein m is 1. In another embodiment, the present invention provides a compound represented by the formula (1), wherein p is 0. In another embodiment, the present invention provides a compound represented by the formula (1), wherein P is 0 and R5 is hydrogen. In one aspect of this embodiment, the B ring is an n-pyridyl or quinoxaline group. In another embodiment, the present invention provides a compound represented by the formula (1), wherein P is 1. In one aspect of this embodiment, R6 is cyano, molybdenum, sulphate, sulfonyl or butoxy. I40628.doc •26·201002728 In another embodiment, the present invention provides a compound represented by the formula (1), wherein P is 1 and R5 is hydrogen. In one aspect of this embodiment, R6 is nitrox, sulfonyl, sulfonyl, sulfonyl or butoxy. In another embodiment, the present invention provides a compound represented by the formula (1), wherein P is 2. In one aspect of this embodiment, each occurrence of R6 is independently selected from the group consisting of cyano, bromo, indolyl, sulfonyl and butoxy.

In another embodiment, the invention provides a compound represented by formula (I) wherein P is 3. In one aspect of this embodiment, each occurrence of R6 is independently selected from the group consisting of cyano, bromo, fluorenyl, fluorenyl and butoxy. In a particular embodiment, the invention provides a compound of formula (1) as described above, wherein: X is CH; L is, C; B i is a bite group; R3 is thiazolyl; wherein the thiazolyl group may be optionally substituted on the carbon by one or more R1Q; r5 is selected from the group consisting of: 1,3,4-oxadiazolyl, 1//_ Tetrakidenyl, 1,3,4-thiadiazolyl, ugly-1,2,4-triazolyl, 1,2,4-oxadiazolyl, 4,5-dihydro-oxazolyl , 1 ugly-pyrazolyl, 2-sided oxy-3//-1, 2, 3, 5-. Ethylpyrazole, 丨//-imidazolyl and morpholinyl; wherein the oxadiazolyl, 1 仏tetrazolyl, 1,3,4-thiadiazolyl, 1//-1, 2 , 4-triazolyl, I2,4-oxadiazolyl, 4,5-dihydro-oxazolyl, 1/--pyrazolyl, 2-sided oxygen 140628.doc -27- 201002728 base-3 ugly -1,2'3,5. oxathiadiazolyl, 1 孖-imidazolyl and morpholinyl may optionally be substituted by one or more R14 on one or more carbon atoms; and wherein 1//-tetrazole The thiol group, the thiol group, the imidazolyl group, the morpholinyl group or the fluorene group may be optionally substituted with a methyl group; the difluoromethylpyridyl group, the phenyl group, and the _Mercapto-1//pyrazolyl; m is 0; and p is 0. In a particular embodiment, the invention provides a compound of formula (I) as described above, wherein: X is CH; Is a -Csc-; B ring is ° ratio bite; R is Cl-4 appearance; R2 is hydrogen; r3 is pyridyl; R5 is selected from the group consisting of: 13,4-oxadiazolyl , 1 good _ 4 ° sitting base, 1,3,4-thiadiazolyl, 1 open _1,2,4-triazolyl, 1,2,4-oxadiazolyl, 4,5-dihydrogen -oxazolyl, 1/--pyrazolyl, 2-sided oxy-3//-1, 2,3,5-° sulphur . a base group, a 1-imidazolyl group and a morpholinyl group; wherein the 1,3,4-oxadiazolyl, 1/--tetrazolyl, 13,4-thiadiazolyl, triazolyl, 1, 2,4-oxadiazolyl, 4,5-dihydrooxazolyl, pyrazolyl, 2-hydroxyl_3,1,2,3,5-oxathiadiazolyl, 1//- Imidazolyl and morpholinyl may optionally be substituted by one or more R 14 on one or more carbon atoms; and wherein 1 is tetrazolyl, 1 pyrazolyl, imidazolyl, morpholinyl or triazolyl 140628 .doc -28 * 201002728 The -nh- portion may be replaced by a thiol group; m is 〇; and p is 0. I- - In a specific embodiment, the invention provides a compound having the structural formula (1) as described above, wherein: X is CH; L is -Csc_; B ring is 吼β-based; 〇... is ^"alkyl; R2 Is a hydrogen; the ruler 3 is a pyridyl group; the R is selected from the group consisting of 5-hydroxy-indole, 3,4-oxadiazol-2-yl; m is 0; and p is 0 〇 in a specific embodiment The present invention provides a compound having the structural formula (I) as described above, wherein: ϋ X is CH; L is 'C5C-; Β is π-based;

R1 is CK4 alkyl; R2 is oxygen; R3 is gas; R5 is selected from the group consisting of oxadiazolyl, tetrazolyl, 1,3,4-thiadiazolyl, 1//- 1,2,4-triazolyl, ls2,4-oxadiazole 4,5-hydro-oxazolyl, 1/--pyrazolyl, 2-sided oxy-3/^, 2,3 , 5-140628.doc -29- 201002728 ° 嗟 嗟 D 坐 、, 177- 咪 基 及 吗 吗 ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; , 3,4-thiadiazolyl, W-H4·triazolyl, I,2,4-oxadiazolyl, 4,5-dihydro-oxazolyl, pyrazolyl, 2-sided oxy- 3 -1,2,3,5-oxathiadiazolyl, if imidyl and morpholinyl may optionally be substituted by one or more substituents on one or more carbon atoms; and wherein i _ tetrazolyl, The -NH- moiety of 1 pyrazolyl, 17/-imidazolyl, morpholinyl or 1/M,2,4-triazolyl may be optionally substituted by methyl; m is 0; and p is 0 in one The present invention provides a compound having the structural formula (1) as described above, wherein: X is CH; L is -CsC_; B ring is pyridyl; R1 is cv4 alkyl; R2 is hydrogen; R3 is hydrogen; a group of 3,4-oxadiazole-2-alkyl groups; R5 selected from the group described above structural formula (I) consisting of 5-hydroxy-m square; and p is 0. In a particular embodiment, wherein: X is CH; 140628.doc • 30· 201002728 B ring is a bite base;

R1 is cN4 alkyl; R2 is hydrogen; R is trimethylsulfonyl; r5 is selected from the group consisting of: 1,3,4-oxadiazolyl, 1 dan-4-tetrazide, 1,3,4-thiadiazolyl, 1//-1,2,4-triazolyl, 1,2,4-oxadiazolyl, 4,5-dihydro-oxazolyl, 1// -pyrazolyl, 2-oxooxy-3/7-1, 2,3,5-° oxalic"soxadiazole, 1-open-imidazolyl and morpholinyl; wherein these 1,3,4 - oxadiazole f group, 1//-tetrazolyl, H4-thiadiazolyl, l/f-1,2,4-triazolyl, 1'2,4-oxadiazolyl, 4,5 _Dihydro-oxazolyl, ι//_pyrazolyl, 2•xyloxy-3, 1,2,3,5-oxathiadiazolyl, 1//-imidazolyl and morpholinyl In the case of one or more carbon atoms substituted by one or more Ri4; and wherein tetrazolyl, pyrazolyl, 1-open-imidazolyl, morpholinyl or 1/-1,2,4-triazolyl The -NH- moiety may be substituted by a thiol group; m is 〇; and / ^ P is 0. L/ In a particular embodiment, the invention provides a compound of formula (1) as described above, wherein: X is CH; L is -CsC-; B ring is pyridyl;

Rl is Cw alkyl; r2 is hydrogen; R3 is trimethyldecyl; 140628.doc • 31-201002728 'i, 3,4-noxadiindole-2-group consisting of the present invention provided as described above The structural formula R is selected from the group consisting of a 5-perylene group m is hydrazine; and P is 0 〇 in a particular embodiment, wherein: X is CH; L is -C ξ c _ ; B ring is pyridyl; P is 1 ;

R1 is c, _4 alkyl; R2 is hydrogen; and is thiazolyl; wherein the thiazolyl group may be substituted by one or more on carbon; R5 is hydrogen; = is an amine "yl, thiol, cyano" Or a dentate group; R, is trifluoromethylpyridyl, phenyl, 1-methyl-1//-pyrazolyl; and m is 〇0. In a particular embodiment, the invention provides a structure as described above A compound of the formula (1), wherein: χ is CH; L is -Csc_; B is pyridyl, quinoxalinyl or 5,6·dihydro[13]thiazolo[4,5_β 嚷°秦-4,7_ Diketone

R1 is C, _4 alkyl; 140628.doc -32- 201002728 R is nitrogen; R3 is (tetra); wherein the (iv) group may be substituted on carbon by one or R1Q; R is gas; R10 is trifluoromethylpyridine Base, phenyl, methyl-1/7-pyrazolyl; m is hydrazine; and p is 0. The terpine compounds of the present invention are exemplified by the compounds, and the pharmaceutically acceptable salts thereof, each of which provides a further independent aspect of the present invention. In another embodiment, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. In another aspect, the invention provides a process for the preparation of a compound of formula (1) or a pharmaceutically acceptable salt thereof, wherein unless otherwise specified, the variable group in the lower stream is as in the formula ( Defined in j). In general, the compound of the present invention can be coupled to Suzuki by a palladium-catalyzed Suzuki derivative of (1) or (v) with a halogen or a trifluorophthalic acid-derived derivative (ii) or (iv). (as shown in Schemes I and II) 'Subsequent to the addition of an alkenyl bond or an alkynyl bond (and others) and a Hek reaction or a Sonogashira reaction of the R group ( See the scheme in' formulas (la) and (ib) for preparation. Usually the 'eucalyptus coupling reaction is carried out by heating and in the presence of a base such as CS2C〇3. Formula (la) or (lb) may be hydrogenated using a hydrogen source such as hydrogen and a metal catalyst such as a platinum, a ruthenium, a ruthenium or a nickel catalyst to form a compound of the invention having a stretch-bonded R3 group (process) ΠΙ, formula (Ic)). 140628.doc -33- 201002728 Tube Process III shows the addition of 4丞 and the heck or the head reaction of the hydrazine-based bond after the Suzuki coupling reaction, but the reactions can be carried out in another order.

Process I

X1 is a halo or triflate group. γ is a halogen group. R and R are each independently an alkyl group, or R21 and R22 are the same I can be opened/formed into a cyclic acid ester such as 4,4,5,5,4-tetramethyl-Hi diboron-2-yl .

Process II

X is a _ group or a trifluorosulfonate group. 7 is a halogen group. R2丨 and R22々 are each independently an alkyl group, or R2 and R22 together with -OBO- can be formed, a pentyl Ip-acid ester such as 4,4,5,5,-tetramethyl-13 , 2-dioxaborom-2-yl. 14〇628.d〇c -34- 201002728 f

Process III

The halogen derivative and the diboron compound (such as 4, 4, 4', 4' can be heated by heating in an organic solvent in the presence of ruthenium, bismuth(bisphenylphosphino)ferrocene-palladium dichloride, 5,5,5',5'-octadecyl-2,2'-linked (1,3,2-dioxaborane)) to prepare a derivative of the acid. 140628.doc -35- 201002728 The glandular portion of the compound of the present invention may be derived from an isocyanic acid derivative prior to or after the eucalyptus coupling reaction (as shown in the rhyme money) or after (4) Biological preparation. If the Suzuki coupling reaction or _l_r3 addition is carried out before the urea formation, the 'amine protecting group protects the amine. As shown in the scheme ^, when the urea is formed into a urea-like organism, the oleic acid derivative (V(1) disc amine derivative (10) is usually combined in an organic solvent and heated. The solvent may be aqueous, organic solvent or water-based. A mixture of miscible organic solvents and water.

Process IV

When R is a heterocyclic group, it can be added by a eucalyptus coupling reaction similar to that which is not carried out in the schemes and hydrazines. R5 may be coupled to the b ring before or after the anthracene ring and the a ring, month] or after the addition of M_l_r3. Alternatively, 's R A heterocyclyl, which can be afflicted from an ester derivative before or after coupling of the B ring to the octacyclic ring. Spot/, for example, when R is a thiazolyl group, the ester derivative can be converted to the guanamine (1) by treatment with a solution in an alcohol. The indoleamine derivative (1) can then be converted to the thioguanamine (9) by treating the indoleamine with Laughssons reagent. The thiobenzamine (f) is then heated with a 4 ketone or a ketone, and then treated with an acid such as trifluoromethane to form a thiazole (see Scheme V). Although the % solution is prepared by coupling the A ring to the 8-ring eucalyptus, it can also be prepared after the coupling reaction of the ester derivative. Similarly, the R thiazole % can be prepared before or after the addition of r3_l_ to the A ring.

Process V

丄, ^7 machine roll 2 3 R is hydrogen or, as the case may be substituted.

When R5 is tetra-recorded, it can be reacted as shown in VI by heating the cyano-based organism with sodium azide and ammonium chloride in a solvent to achieve the reaction shown in the heart-path 7 before the coupling of the ring B and the ring A or Prepared before or after = R -L-.

Process VI

140628.doc -37- 201002728 The base is treated with a base to form a carboxylic acid (xvii). Next, the tickic acid (xvii) is coupled with the anthracene derivative (4) (1) in the presence of a guanamine coupling reagent HATU to form a diterpene derivative (xix). As shown in the scheme νπ, the second series (XIX) is treated with triphenylphosphine in an aprotic organic solvent in the presence of 35 amounts of a non-plasma to form an R group of 13,4 oxadiazolyl. Inventive compound h magic. The R 1,3,4_° oxazolyl group can be prepared by the reaction shown in Scheme VII before or after coupling of the anthracene ring to the a ring or before or after the addition of R3_L·.

Process VII

PPh3 aproton test

When R5 is 1,3,4-indolyl, it can be prepared from a diterpene derivative (xix) (see Scheme VII for the preparation of a diterpene derivative). As shown in Scheme VIII, the dioxan derivative (xix) is heated with an organic solvent in the organic solvent to form R5 1,3 with phosphorus pentasulfide and hexamethyldiazepine 140628.doc -38-201002728. , 4_thiadiazolyl of the present invention (xxi). R5丨'3,4-thiadiazolyl can be prepared by the reaction shown in Scheme νπι before or after coupling of the anthracene ring to the anthracene ring or before or after the addition of _L_R3.

Process VIII

When R5 is 2-sided oxy-1,3,4-oxadiazolyl or 2-thioketo-1,3,4-oxadiquinone. It can be prepared from a carboxylic acid (xvii) when sitting on a base (see Process VII for the preparation of a carboxylic acid derivative). The carboxylic acid derivative (xvii) is heated together with hydrazine hydrate in an alcohol to form an anthracene derivative (xxii). As shown in the scheme, the anthracene derivative (XXII) is then combined with carbonyldiimidazole or bis(1-indole-imidazolium-2-yl)thione (χχίϋ) in an aprotic solvent in the presence of an aprotic solvent. The reaction is carried out to form a compound of the present invention (xxiv) having Rs 2 • pendantoxy-1,3,4-oxadiazolyl or 2-thioketo-H4-oxadiazolyl. R5 2-sided oxy-H4-oxadiazolyl or 2-thiol-1,3,4-oxadiazolyl can be preceded or after coupling of ring B to a ring by the reaction shown in Scheme Ιχ Or prepared before or after the addition of -L-R3.

Process IX

140628.doc -39· 201002728 oxo base X4 is o or s. (xxiii)

When R is a 1,2,4-diazolyl group, it can be derived from a decylamine derivative (χχν) by a network of 1-(N,N-dimethylamino)methoxy-ethane (xxvj). The addition fee is prepared by forming (xxWi). As shown in the scheme, the compound (xxvii) is then heated with acetic acid in acetic acid to form a compound of the present invention (xxviii) having r5丨,2,4-trisal. The r5 can be prepared by the scheme for the reaction shown before or after coupling of the B ring to the A ring or before or after the addition of _l R3. When R is 1,2,4-anthracenyl, it can be obtained by subjecting (XXWi) with hydrochloric acid to amine in acetic acid (in di-burning) as shown by the scheme. Heating in the mash to form the compound of the present invention (XXiX) having the rule 5 as i, 2 4 嗯 唾 基 来 来 可 可 可 可 can be prepared by the reaction shown in the scheme X before or after the coupling of the anthracene ring and the anthracene ring Or before adding Μ; prepared before or after. 140628.doc -40- 201002728

Process x

ΙλΛΙΧ) When R5 is an imidazolyl group, 1 is ή/, and the cyano derivative (xiv) is derived from a cyano group.

The organism (iv) was prepared by stirring in a solution of methanol in methanol at room temperature for several hours. As shown in Scheme xIt, dimethoxy-2-aminoethane bn) is then added to the solution and heated to give R5 as the imidazolyl = inventive compound (XXXi). The R5 imidazolyl group can be prepared by the reaction shown in Scheme 1 before or after coupling of the B ring to the A ring or before or after the addition of _L_R3. 140628.doc -41 - 201002728

Process XI

The formation of medically acceptable salts is within the skill of a general organic chemist using standard techniques. It will be appreciated that some of the various ring substituents in the compounds of the invention may be introduced by standard aromatic substitution reactions immediately before or after the above process or by conventional functional group modifications to produce '纟 and thus are included in the invention. The method is in vitro. The reagents used to introduce such ring substituents are either commercially available or can be prepared by methods known in the art. A compound of formula (1) can be converted to another compound of formula (I) by introducing a substituent into the ring. Such reactions and modifications include, for example, introduction of substituents by means of aromatic substitution reactions, reduction of substituents, alkylation of substituents, oxidation of substituents, esterification of substituents, amide amination, and heteroaryl ring formation. The reagents and reaction conditions of these procedures are well known in the chemical arts. Specific examples of the aromatic substitution reaction include introduction of an alkoxide, diazotization reaction, followed by introduction of a thiol group, an alcohol group, and a halogen group. Examples of the modification include oxidation of an alkylthio group to an alkylsulfinyl group or an alkylsulfonyl group. Skilled organic chemists will be able to use and adapt the information contained and mentioned in the above references and accompanying examples and examples herein to obtain the necessary starting materials and products. If not commercially available, the essential starting materials for procedures such as those described above in the 140628.doc-42-201002728 procedure may be by techniques selected from standard organic chemistry techniques, similar to synthetic compounds of similar structure, or the like. The program of the techniques described in the above procedures or examples is made. It should be noted that many of the starting materials used in the synthetic methods described above are commercially available and/or widely reported in the scientific literature, or may be prepared from commercially available compounds using methods of modification reported in the scientific literature. General guidance on reaction conditions and reagents' Please refer to Jerry March's Advanced for further reference.

Organic Chemistry, 4th ed. (published by j〇hn Wiley & S〇ns, 1992) 亦 It should also be understood that in some of the reactions mentioned herein, it may be necessary/need to protect any sensitive groups in the compound. It is known to those skilled in the art that it is necessary or necessary to protect, as well as suitable methods for such protection. Conventional protecting groups can be used according to standard specifications (for instructions, see Tw. Greene, Protective Groups in 〇rganic Synthesis, J〇hn viscous 丫 and s〇ns, 1991). Examples of suitable protecting groups for the radical are, for example, fluorenyl groups, for example, alkanoyl groups (such as ethyl hydrazino groups), aryl fluorenyl groups (for example, benzamidine groups); A group, or an arylmethyl group, such as a benzyl group. The removal of the protecting group conditions for the above protecting groups will necessarily vary with the protecting group selected. Thus, for example, a thiol group such as a (iv) group or an aryl acid group can be removed, for example, by hydrolysis with a suitable test such as a metal hydroxide (e.g., sodium hydride hydroxide). Alternatively, a (tetra) group such as trimethyl ketone can be removed, for example, from fluoride or from an aqueous acid; or a benzyl group such as benzyl can be, for example, by a catalyst such as palladium on carbon Hydrogenation in the presence of I40628.doc -43· 201002728 removed. Suitable protecting groups for the amine group are, for example, fluorenyl groups, such as alkanoyl groups, such as ethenyl; alkoxy groups such as methoxy, ethoxy or tert-butoxy; arylmethoxy For example, a benzyloxy group; or an aromatic base such as = formazan. The removal of the protecting group conditions for the above protecting groups must be varied with the selected protective f. Thus, for example, a brewing group such as a porphyrin or a oxyalkyl group or a fluorenyl group can be, for example, carried out by using a suitable base such as a metal hydroxide (for example, lithium hydroxide or sodium hydroxide). Hydrolyzed to remove. Alternatively, a thiol group such as a butyloxy group can be removed, for example, by treatment with a suitable acid such as hydrochloric acid, sulfuric acid or a dish or trifluoroacetic acid, and an aryl methoxy group such as benzyloxycarbonyl Can be removed, for example, by treatment with a Lewis acid such as palladium/carbon as a Lewis acid (e.g., tris(ethylene)). Suitable alternative protecting groups for the first amine group are, for example, defeated. The base can be removed by alkylamine (such as dimethylaminopropylamine or 2,ethylamine) or by hydrazine. Suitable protecting groups for the carboxyl group are, for example, esterification groups such as methyl or ethyl , which can be removed, for example, by hydrolysis with a base such as sodium hydroxide or, for example, a third butyl group, which can be treated, for example, by an acid such as an organic acid such as trifluoroacetic acid. To remove; or, for example, a benzyl group, which can be removed, for example, by hydrogenation over a catalyst such as carbon/carbon; or, for example, a pot can be used, for example, by using a palladium catalyst such as palladium acetate. Removal. The eight protecting groups can be removed from any convenient stage of the synthesis process by knowing the technology to remove 'or Post-reaction step or treatment period shift 140628.doc -44 - 201002728 When a photoactive form of a compound of the invention is desired, it can be carried out by using a photoactive starting material (for example, formed by asymmetric induction of a suitable reaction step) One of the above procedures, or by using a standard procedure to resolve the racemic form or the intermediate in a racemic form or by chromatography to separate the diastereomers (if prepared). Enzymatic techniques are also applicable. For the preparation of optically active compounds and/or intermediates. Similarly, when a pure regioisomer of a compound of the invention is desired, it can be carried out by using a pure regioisomer as a starting material, or It can be obtained by using a standard procedure to resolve a mixture of regioisomers or intermediates. Enzyme potency test method Large-scale r-bacillus (where co//) GyrB ATPase inhibitory activity: can be used based on ammonium molybdate/malachite green Phosphate Detection Assay (Lanzetta, p-A·, L. J. Alvarez, P. s. Reinach, and 〇A Candia, 1979, 100: 95-97) Test compounds for inhibition of E. coli GyrB ATPase activity 3〇 μ1 assay may contain the following reactants by application of the porous plate into the

Row ' 50 mM Hepes buffer (pH 7.5), 75 mM ammonium acetate, 8.0 mM magnesium chloride, 0.5 mM ethylenediaminetetraacetic acid, 5% glycerol,! mM M-dithio-DL-threitol, 200 nM bovine serum albumin, 16 gg/mi sheared salmon sperm DNA, 400 pM E. coli GyrA, 4〇〇pM E. coli GyrB, 250 μΜ ATP And compounds in the wind of the one-way stone. The reaction can be stopped with 3 μ μ μ of ammonium molybdate/malachite detection reagent containing 1.2 mM malachite green hydrochloride, 8.5 mM ammonium molybdate tetrahydrate and 1 guanidine hydrochloride. The plates can be read at 650 nm in an absorbance plate reader and the reaction containing 140 dimethyl hydrazine 140628.doc -45 - 201002728 as a 0% inhibition control and a reaction containing EDTA (2.4 μM) is used as 100 % inhibition control to calculate the percent inhibition value. The IC50 measure of compound potency can be determined for each compound from reactions carried out in the presence of 10 different compound concentrations. E. coli topoisomerase IV ATPase inhibitory activity: The test compound was inhibited against E. coli topoisomerase IV ATPase activity as described above for E. coli GyrB, with the exception that the 30 μΐ reaction contained the following: 20 mM TRIS buffer (pH 8), 50 mM ammonium acetate, 8 mM magnesium chloride, 5% glycerol, 5 mM 1,4-dithio-DL-threitol, 0.005% Brij-35, 5 pg/ml cut shoefish Sperm DNA, 500 pM E. coli ParC, 500 pM E. coli ParE, 160 μΜ ATP and compounds in disulfoxide. The IC5G measure of compound potency can be determined for each compound from reactions carried out in the presence of 10 different compound concentrations. The compound of Example 1 was tested in a assay substantially similar to the above assay for measuring inhibition of E. coli GyrB ATPase and E. coli topoisomerase IV ATPase and it has <200 μΜ in both assays. IC50 value. Staphylococcus aureus GyrB ATPase inhibitory activity: Ammonium molybdate/malachite-based phosphate detection assay can be used (Lanzetta, P. A., LJ Alvarez, PS Reinach, and OA Candia, 1979, 100: 95-97) Test compounds inhibit S. aureus GyrB ATPase activity. The assay can be performed in a multi-well plate in a 30 μΐ reaction containing: 50 mM Hepes buffer (pH 7.5), 75 mM ammonium acetate, 8.0 mM magnesium carbonate, 0.5 mM ethylenediaminetetraacetic acid, 5 % glycerol, 1.0 mM 1,4-dithio-140628.doc -46- 201002728 DL-threitol, 200 nM bovine serum albumin, 1.0 pg/ml sheared parasitic fish sperm DNA, 250 pM large intestine Bacillus GyrA, 250 pM Staphylococcus aureus GyrB, 250 μΜ ATP and compounds in diterpene. The reaction can be stopped with 30 μΐ of ammonium molybdate/malachite detection reagent containing 1.2 mM malachite green hydrochloride, 8.5 mM ammonium molybdate tetrahydrate and 1 guanidine hydrochloride. The plates can be read at 650 nm in an absorbance plate reader and the reaction containing dimethyl sulfoxide (2%) can be used as a 0% inhibition control and a reaction containing EDTA (2.4 μM) as 100%. The inhibition is calculated to calculate the percent inhibition value. The IC5G measure of compound potency can be determined for each compound from reactions carried out in the presence of 10 different compound concentrations. The compound of Example 1 was tested in an assay substantially similar to the above assay for measuring inhibition of S. aureus GyrB ATPase and was found to have 102% S. aureus GyrB ATPase at a compound concentration of 1 μM. Percent inhibition. Bacterial Sensitivity Test Method The antimicrobial activity of a compound can be tested by a sensitivity test in a liquid medium. Compounds can be dissolved in disulfoxide and tested in 10 diploid dilutions in a sensitivity assay. The organism used in the assay can be grown overnight on a suitable agar medium and then suspended in a liquid medium suitable for growth of the organism. The suspension may be 0.5 McFarland and the other of the 10 dilutions is made into the same liquid medium to prepare a 100 μιη final biological suspension. The plates can be incubated at 37 ° C for 24 hr under appropriate conditions and then read. The minimum inhibitory concentration (MIC) can be determined as the lowest drug concentration that can reduce growth by 80% or more. 140628.doc -47- 201002728 In the equivalent of the above, the MIC of μΜ. Column 1 for S. pneumoniae has a formula (1) according to another feature of the invention, a method of body or animal body for the treatment of human salt by therapy. '(1) A compound or a pharmaceutically acceptable compound thereof, in a consistent embodiment, the present invention provides a method for treating an animal such as a human animal, which comprises a method of invigorating the door. The animal or human is administered an effective amount of a compound of the formula (1) or a pharmaceutically acceptable salt thereof. It has been found that the compounds of the invention inhibit the bacterial spirulinase and/or topoisomerase 1V and are therefore concerned with their antibacterial action. In one aspect of the invention, the compounds of the invention are defensed | prawn making fine droplet DNA rotase' and are therefore concerned with their antibacterial action. In one aspect of the invention, the compounds of the invention inhibit topoisomerase IV and are therefore of interest for their antibacterial action. In the aspect of the present invention, the compound of the present invention inhibits DNA gyrase and topoisomerase IV and is therefore concerned with its antibacterial action. Because of &, the compounds of the invention are useful for treating or preventing bacterial infections. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection initiated by Bowman's inactive bow. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by hemolysis without treatment/mewo/yhcw·?). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Acinetobacter junii. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Acinetobacter johnsonii /o/zwoWz.). In one aspect of the present invention, 140628.doc -48-201002728, "infection" or "bacterial infection" refers to an infection caused by Acinetobacter ruta (4)/Li). In one aspect of the invention, "sensible wood" or "bacterial infection" refers to an infection caused by Bifidobacterium bifidum hwMi). In one aspect of the present invention, "infection" or bacterial sensation refers to an infection caused by Bacteroides fragilis (in this case, sighs//). In one aspect of the invention, "infection" or "bacterial infection" is caused by Burkholderia cepacia (infection caused by 10,000. In one aspect of the invention, "infection" or "bacterial infection" "" refers to an infection caused by Aspergillus niger »m·). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by P. pneumoniae (C/2/amMM • postal). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by a solution to the urea-coating bacteria. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Chlamydia pneumoniae (c/2/aw> VI. In one aspect of the invention, "infection" or "Bacterial infection" refers to an infection caused by Clostridium faecalis (c/(10)·山·_山万'/c//e). In one aspect of the invention, "infection" or fine-faced infection ” refers to the infection caused by Enterobacter aerogenes (5 „ier (?6acier infection. In one aspect of the invention, “infection” or “bacterial infection” refers to the infection caused by Enterobacter cloacae c/oacae) In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Enterococcus faecalis (five _r〇C〇CCWly. In one aspect of the invention, "infection" or "infection" Bacterial infection J refers to an infection caused by Enterococcus faecium. In one aspect of the present invention, "infection" or "bacterial sensation 140628.doc ACi 201002728 dyeing" refers to the political water caused by E. coli. In one aspect of the present invention, "feeling Zhu" or "bacterial wei + sun", ', Japanese vaginal Gardnerella (Gar^ere / / (2 V coffee:), caused by the sense In the aspect of the present invention, "infection" or fine/infection refers to an infection caused by Haemophilus parainfluenzae (valence (4) 叩/n7w biliary e). In the aspect of the present invention, "Sense of wood" or ", Tiantian infection" refers to an infection caused by influenza bacillus (Pseudocalyx, heart n//Me «zae). In the aspect of the invention, "infection or "bacteria" "Infection" refers to an infection caused by Helicobacter pylori (IV). In one aspect of the invention, "infection" or "bacterial infection" refers to Klebsiella pneumoniae (10) palpitations "" Infection according to one aspect of the present invention, "infection" or "bacterial infection" is an infection caused by a lunge-deprived Veterans bacillus (Zeg/〇we//a (10) is noisy wm). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by methicillin-resistant Staphylococcus aureus. In one aspect of the invention, "infection" or "bacterial infection" "" refers to an infection caused by methicillin-sensitive Staphylococcus aureus. In one aspect of the invention "Infection" or "bacterial infection" means an infection caused by Moraxella catarrhalis (Mc»raxe//a caiarr/m/b). In one aspect of the invention, "infection" or "bacterial infection" "Infection caused by Morse a'e//a. In one aspect of the invention, 'infection j or 'bacterial infection' means an infection caused by M. pneumoniae. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by gonorrhea (iVez'werz'a. In one aspect of the invention, "infection" 140628.doc -50 - 201002728 or "bacterial infection" means an infection caused by Streptococcus pneumoniae resistant to penicillin. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by penicillin-sensitive Streptococcus pneumoniae. In one aspect of the present invention, "infection" or "bacterial infection" refers to an infection caused by Streptococcus pallidum (Pepiowrep/ococcwj. In a bear sample of the present invention, 'infection' or "bacterial infection" Refers to an infection caused by S. difficile (PepioWrepiococcw-like). One of the bears of the present invention

In the sample, "infection" or "bacterial infection" refers to an infection caused by anaerobic digestion of Streptococcus (Pepiowrepiococcw. In one aspect of the invention, "infection" or "bacterial infection" refers to the digestion of the sugar chain. In the aspect of the present invention, "infection" or "bacterial infection"::: a feeling caused by Streptavidin (Pepi〇>^repi〇C〇CCWiy prev) is one aspect of the present invention. "Infection" or "bacterial infection" is caused by (10) mountain-like illness. In one aspect of the invention, 'infection' or "bacterial infection" means In the aspect of the present invention, "infection" or "bacterial infection" refers to an infection caused by Proteus mirabilis (/Vokw. One of the inventions) In the case of a bear, "infection" or "bacterial infection" refers to an infection caused by a green rod '= (PMMciom (10) like aerwgbwa). In the present invention, the "infection" or "bacterial infection" system Refers to infection caused by anti-quino g and Staphylococcus aureus. One of the inventions In the sample, "''~7 T , infection " or "bacterial infection" refers to dyeing by the epidermal grape ball against quinolone, and the feeling of I _ W I40628.doc -51 - 201002728. In the state of the present invention In the sample, "infection" or "bacterial infection" refers to infection caused by Salmonella typhimurium (仏/m(10)β//β. In one aspect of the invention, "infection" or "bacterial infection" refers to paratyphoid fever. Salmonella (infection of heart/mo/M. In one aspect of the invention, "infection" or "bacterial infection" refers to Salmonella enteritidis (in /m(10)d/α ewieWi/c/) In one of the present invention, "infection" or "bacterial infection" refers to an infection caused by Salmonella typhimurium (*Sa/mo«e//a. In one of the inventions, "Infection" or "bacterial infection" means an infection caused by Serratia marcescens. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Staphylococcus aureus. In one aspect of the invention, "infection" or "bacterial infection" refers to a disease caused by Staphylococcus epidermidis. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Staphylococcus aureus (valuation / 〇c〇a. In one aspect of the invention, "infection" Or "bacterial infection" means an infection caused by Streptococcus agalactiae (A. flchae). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Streptococcus pneumoniae. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Streptococcus pyogenes. In the bear sample of the present invention, "infection" or "bacterial infection" means The infection caused by Streptomyces faecalis (5^«〇以〇户/2〇所〇). In the state of the present invention, "infection" or "fine infection" refers to infection caused by Mycoplasma dysentery (t/reflf/?/like. In the aspect of the present invention 140628.doc -52- 201002728 Sense of sensation: in: 囷 infection refers to infection by the anti-vancomycin 屎 」 系 系 : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : The golden yellow grape and the '卞' in the hair of the hair are resistant to the infection of the ancients. In one aspect of the invention, the infection caused by the bacteria. In this:": Vancomycin epidermis grape ball L-mycobacteria (10) 4 coffee (10) - (d)) caused by infection. In the sadness of this month, the "infection" or "bacterial sensation, the genus Clostridium perfringens (C / o other oil / (4) per / w « g (4)) caused by = in one aspect of the invention "Infection" or "bacterial infection" is an infection caused by Klebsiella pneumoniae (10) heart " alpha (10)). In the aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by brain *, human and cocci _ heart " In the heart of the present invention, "infection" or "bacterial infection" refers to an infection caused by the genus Clostridium (small bacterium). In one aspect of the invention, "sensible wood" or "bacterial infection" refers to an infection caused by the genus Digestive genus W.). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by a common proteobacteria (corpse vw/...): in one aspect of the invention, "infection" or "bacterial infection" Means by coagulase-negative staphylococci (including Staphylococcus aureus (known as hgdu_sis), Staphylococcus aureus (Staphyi〇c〇ccus c, called Staphylococcus aureus (5V叩/2 less/OCOCC(10) and saprophytic Infections caused by Staphylococcus aureus. 140628.doc -53- 201002728 In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by a genus of a moving cup (W.). In one aspect, "infection" or "bacterial infection" refers to an infection caused by Bacteroides vp.). In one aspect of the invention, "infection" or "bacterial infection" refers to Berkshire. Infection caused by genus. In one aspect of the present invention, "infection" or "fine sensation h" is caused by the sputum; In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Pelican #p). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Chlamydia. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Clostridium (c/(10)(4)). In the aspect of the invention, "infection" < "bacterial infection" means an infection caused by the intestinal genus. In one of the evil samples of the present invention, "% of infection "纟s g g , : J , ·, 田国砍木" refers to an infection caused by Enterococcus (仏加〇C〇CCWi 5中_). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by the genus Escherichia. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by the genus Gardnerella (sigma). In the aspect of the invention, "infection is caused by "bacterial infection" Means that one of the aspects of the present invention is caused by Haemophilus (7) ae_^qing), "remaining 1 Γ 4 4 in + chopping wood" or fine sputum infection" means by the spiral, ... "infection. In the present invention, the sensation or fine sensation is applied. ih rK i chopping wood is an infection caused by Klebsiella sp. I40628.doc -54·201002728. In the present invention, _ | τ ^ dyeing or "bacterial infection" refers to an infection caused by Legionella (£eg/owe...). In one aspect of the present invention, "infection" or "fine sensation ^" refers to an infection caused by Moraxella (from π corpse _). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by a Morganella genus. In one aspect of the present invention, "infection" and "bacterial infection" refer to an infection caused by a mildew (four) genus (such as a coffee). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by a bacterium. In the context of this month, "infection" or "bacterial infection" refers to an infection caused by the genus Streptococcus. In the aspect of the invention, "infection" or "bacterial infection" means an infection caused by Proteus (Proiewi.). In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Pseudomonas (4). In one aspect of the invention, "infection" or "fine infection" refers to infection caused by Salmonella genus. In one aspect of the invention, ".infection" or bacterial infection means an infection caused by the genus Serratia (☆rrflhcr 〇 '^丨*, 士沙·). In one aspect of the present invention, "infection" or "fine 喆^ 固固木" means ❹ which is caused by Staphylococcus (": (10)w.) 5. In the present invention, "卞" Or "bacterial sensation*" refers to the "infection" or "fine sensation" in the form of the genus Streptomyces (Additional willow (10) (10) - 戌 ^ ^ ^, refers to the cultivation of monosaccharides, ,,, It belongs to {htenotrophomonas spp., 1^. In one of the inventions, "infection" or "bacterial sensation 140628.doc -55. 201002728 dyeing" refers to the genus Ureaplasma s/Ψ· ) caused the infection. In the aspect of the invention, "infection" or "bacterial infection" means an infection caused by aerobic bacteria. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by an obligate anaerobe. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by facultative anaerobe. In one of the aspects of the present invention, "infection" or "bacterial infection" refers to an infection caused by Gram-positive bacteria. In one aspect of the invention, "infection" or "bacterial infection" refers to an infection caused by Gram-negative bacteria. In one embodiment of the invention, "infection" or "bacterial infection" refers to an infection caused by Gram's variable bacteria. In one aspect of the invention, 'r infection' or 'bacterial infection' refers to an infection caused by an atypical respiratory pathogen. In the present invention, "infection" or "bacterial infection" refers to an infection caused by intestinal g. In one aspect of the invention, "infection" and "bacterial infection" refer to infections caused by Shigella bacillus. In the aspect of the invention, "infection" or "bacterial infection" means an infection caused by the genus Citrobacter. In one aspect of the invention, "infection" or "bacterial infection" refers to a gynecological infection. In one aspect of the invention, "infection" or "bacterial sensation" refers to a beer suction infection (RTi). In the aspect of the invention, "infection" or "bacterial infection" refers to a sexually transmitted disease. In one aspect of the invention, "infection" 4 "bacterial infection" refers to a urinary tract infection. In the present invention, "infection" or "bacterial infection" refers to each of chronic bronchitis: deterioration. In the aspect of the invention, "infection" or "bacterial sensation 140628.doc * 56 - 201002728 dyeing" refers to acute middle ear; ^ ", & in one aspect of the invention, "salt, or "Bacterial infection" means "injury province' mf "J ^ ^ Γ ~, sinusitis. In one aspect of the invention, "sense wood" or a bacterial bacterium escapes, 0^^ "'," 糸s infection caused by drug-resistant bacteria. In one of the symptoms of this month, "醴主广士丄4木" or bacterial infection" is a guide to tube related purulent diseases. One of the features of the invention can be referred to as a soft chin. In the case of too ~, infection or "bacterial infection", t ^ in one aspect, "infection" or "bacterial sensation" in the aspect of the invention, "infection" or "fine

"/Jiuyuping pneumonia (CAP). In one aspect of the invention" or "bacterial infection" refers to a concomitant skin and skin structure infection. In the present invention, "infection" or "bacterial infection" refers to a non-concurrent skin and skin structure infection. In one aspect of the invention, an infection or bacterial infection refers to endocarditis. In the present invention, "sensible wood" or "bacterial infection" means febrile neutropenia. In one aspect of the invention, "infection" or "bacterial infection" refers to gonococcal cervicitis. In one aspect of the invention, "infection" or "bacterial infection" refers to gonococcal urethritis. In one aspect of the invention, sputum infection or "bacterial infection" refers to hospital-type infectious pneumonia (ΗΑρ). In one aspect of the invention, "infection" or "bacterial infection" refers to osteomyelitis. In one aspect of the invention, "infection" or "bacterial infection" refers to a sepsis. In one aspect of the invention, "infection" or "bacterial infection" refers to syphilis. In one aspect of the invention, "infection" or "bacterial infection" refers to sputum-associated pneumonia. In one aspect of the invention, "infection" or "bacterial infection" refers to an intra-abdominal infection. In one aspect of the invention, "defective" or "bacterial infection" refers to gonorrhea. In one aspect of the invention, 140628.doc -57-201002728 sensible wood or yam yam infection refers to meningitis. In one of the present inventions, "infection" or "bacterial infection" refers to tetanus. In the case of the j cancer of the present invention, "infection" or "bacterial infection" means tuberculosis. In the case of ' _ this hair day and month compound will be suitable for infection, including (but not PP recognition,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Acute exacerbation, acute sinusitis, acute otitis media, catheter-related arrhythmia, cyanosis 2: bone inflammation, endocarditis, urinary tract infection and by: medicine; the sense of bacteria * 抗 and other drug-resistant bacteria Such as pneumococcal sputum resistant to penicillin, Staphylococcus aureus resistant to dimethoprim, Staphylococcus epidermidis resistant to dioxylbinomycin, and Enterococci against vancomycin. According to another aspect of the invention - A method of providing an antibacterial effect in a warming action, such as a male, in need of treatment, which comprises administering to the animal an effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof. According to still another feature of the present invention, there is provided a method of inhibiting a bacterial sputum gyrase and/or topoisomerase IV of a warm blooded substance (such as a human) in need of treatment comprising administering to the animal an effective amount as above A compound of formula (1), or a pharmaceutically acceptable salt thereof, as defined. According to still another feature of the present invention, there is provided a method of treating a bacterial infection of a warm blood: a substance (such as a human), comprising administering to the animal a compound of formula (J) as hereinbefore defined or Its medicinal salt can be connected. According to another feature of the invention, there is provided a method of treating a bacterial infection selected from the group consisting of a warm blood (such as a human) in need of treatment: Community I40628.doc -58- 201002728

Type of infection pneumonia, hospital-type infection pneumonia, skin and skin structure infection, acute exacerbation of chronic bronchitis, acute sinusitis, acute otitis media 'catheter sepsis, febrile neutropenia, osteomyelitis, heart Endometritis, urinary tract infections, and infections caused by drug-resistant bacteria such as Streptococcus pneumoniae resistant to penicillin, Staphylococcus aureus resistant to methicillin, and epidermal grape resistant to methicillin Cocci and vancomycin-resistant enterococci 1 comprise administering to the animal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as hereinbefore defined. Another characteristic of the present month is the compound of the formula (I) and a pharmaceutically acceptable salt thereof for use as a medicament. The drug is suitably an antibacterial agent. According to another aspect of the present invention, there is provided a use of a compound of the formula (1) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for action in a warm-blooded animal such as a human. According to another aspect of the present invention, there is provided a compound of formula (I) or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for inhibiting bacterial gyrase and/or topoisomerase IV of a warm-blooded animal such as human Use in. The invention thus provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of bacterial infections in warm-blooded animals such as humans, according to another aspect of the invention. Therefore, according to another aspect of the present invention, there is provided a compound of the formula (1) or a salt thereof, for use in the manufacture of a medicament for treating a warm-blooded animal such as a human, the bacterial infection system Selected from the Du District infection tube: it::! Infection with pneumonia, skin and skin structure infection, chronic bronchial gasification, chemotherapy, acute inflammatory inflammation, acute otitis media, catheter-related pus. 140628.doc -59- 201002728 'Fever neutropenia, osteomyelitis, intracardiac Membrane inflammation, urethra? 711 丨 丨 细 细 细 ' § § § § 荨 § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § § Staphylococcus epidermidis and vancomycin-resistant enterococci. According to another aspect of the present invention, there is provided a compound of the formula (1) for use in the production of a sputum bacterium in a warm gold animal such as a human or a pharmaceutically acceptable hydrazine thereof according to another aspect of the present invention. A formula (1) for inhibiting bacterial DNA gyrase and/or topoisomerase IV of a warm-blooded animal such as human or a pharmaceutically acceptable salt thereof. σ Thus, according to another aspect of the present invention, there is provided a compound of the formula (1) or a pharmaceutically acceptable salt thereof for use in the treatment of a bacterial infection of a blood-sucking animal such as a human. Further, according to another aspect of the present invention, there is provided a compound of the formula (1) or a pharmaceutically acceptable salt thereof for use in the treatment of a bacterial infection of a warm-blooded animal such as a human, the fine g-sensation (4) being selected from the group consisting of Infected pneumonia, hospital-type infections: inflammation, skin and skin structure infections, acute exacerbation of chronic bronchitis, acute sinusitis, acute otitis media, tube-related sepsis, febrile neutropenia, osteomyelitis, heart Endometritis, urinary tract infections, and infections caused by drug-resistant bacteria such as Pneumococci against Penicillin, Staphylococcus aureus resistant to methicillin, and Epidermal grapes resistant to methicillin Ball® and the anticoccidial enterococci. For the therapeutic (including prevention) of a compound of the formula (!) or a pharmaceutically acceptable salt thereof (hereinafter referred to as "the compound of the present invention" in this part of the composition of 140628.doc-60-201002728 W Le) Treatment) includes mammals in humans, especially for the treatment of infections, which are usually formulated into pharmaceutical compositions according to standard pharmaceutical practice. Thus, in another aspect, the invention provides a pharmaceutical composition comprising a compound of formula (1), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. According to another aspect of the present invention, there is provided a pharmaceutical composition, which comprises a compound of the formula (1) as defined above, or a pharmaceutically acceptable pharmaceutically acceptable excipient or carrier thereof, which is used in the pharmaceutical composition. It produces an antibacterial effect in warm-blooded animals such as humans. In a further aspect of the invention, there is provided a pharmaceutical composition comprising a compound of formula (1) as defined above, or a pharmaceutically acceptable step, acceptable excipient or carrier thereof, A compound of the formula (1) or a pharmaceutically acceptable salt thereof for use in a pharmaceutical composition, according to another aspect of the invention, for use in a human blood-blooded animal. And an excipient or a carrier for treating a bacterial infection of a blood vessel animal. Another aspect of the invention provides a pharmaceutical composition comprising - a compound of formula (1) or a pharmaceutically acceptable compound thereof, or a pharmaceutically acceptable meaning, and a treatment such as human: ::: The pharmaceutical composition is used for the treatment of infections of pneumonia, bacterial infections of the following types: community i sense of silicosis k, skin and skin structure infection, slow i40628.doc -61 - 201002728 Acute exacerbation of inflammation, acute rule, acute otitis media, catheter phase sputum sepsis, febrile neutropenia, osteomyelitis, endocardial urinary tract infection, and infection caused by drug-resistant bacteria, such resistance For example, Streptococcus pneumoniae resistant to penicillin, Staphylococcus aureus which is resistant to dimethoprim, and Staphylococcus aureus which is resistant to vancomycin and vancomycin against vancomycin. The composition of the present invention can be suitably formulated. In the form of: oral administration (for example, in the form of lozenges, buccal, hard or soft capsules, aqueous or oily suspensions, dispersible powders or granules, syrups or elixirs), 吏...吏Use (eg king cream, ointment, condensate Glue or aqueous or oily solution or suspension solution, inhalation administration (for example, in the form of a fine powder or liquid aerosol, such as in the form of a fine powder) or parenteral administration (for example, in the form of a vein) Sterile aqueous or oily solution for internal, subcutaneous, intramuscular or intramuscular administration or suppository for rectal administration). It can be obtained by using the known medicines known in the art. ♦The composition of the invention. Accordingly, the composition intended for oral use may have, for example, one or more coloring agents 'sweeteners, flavoring agents and/or preservatives. Pharmacologically acceptable for use in lozenge formulations Suitable excipients to be accepted include, for example, inert diluents such as lactose, sodium carbonate, calcium phosphate or calcium carbonate, granulating and disintegrating agents such as corn starch or alginic acid; adhesions such as ageing, lubricants , such as magnesium stearate, stearic acid or talc; preservatives such as ethyl p-hydroxybenzoate or propyl p-hydroxybenzoate; and antimony oxidizing agents such as ascorbic acid. The formulation of the tablet may be uncoated or Package 140628.doc •62- 201002728 The disintegration and subsequent absorption of the active ingredient in the gastrointestinal tract, or the improvement of its stability and/or appearance, in either case, the use of conventional coating agents and procedures well known in the art. The composition may be in the form of a hard gelatin capsule in which the active ingredient is mixed with an inert solid diluent (for example, calcium carbonate, calcium phosphate or kaolin) or is active as a wound with water or oil (such as peanut oil, liquid stone soil or oil Mixed soft gelatin capsule form. Aqueous suspensions generally contain the active ingredient in the form of a fine powder with one or more suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, brown lacquer Sodium, polyethylene-n-bipirone, tragacanth and gum acacia; dispersing or wetting agents, such as lecithin, or condensation products of oxidized olefins with fatty acids (eg, polyoxyethylene stearin) Ethyl ester, or a condensation product of ethylene oxide with a long-chain aliphatic alcohol (for example, hepta-ethyloxy decyl/alcohol), or a partial ester of ethylene oxide with fatty acids and hexitols Condensation product For example, polyoxyethylene sorbitan monooleate, or a condensation product of ethylene oxide with a long-chain aliphatic alcohol (for example, hepta-ethyloxyhexadecanol), or ethylene oxide and derivative a condensation product of a partial ester of a fatty acid and a hexitol, such as polyoxyethylene sorbitan monooleate, or epoxy B, with a partial vinegar derived from a fatty acid and a hexitol anhydride (for example, Polyethylene sorbitol liver monooleic acid g). An inert suspension may also contain - or a preservative (such as 'p-hydroxybenzoic acid ethyl ester or para-hydroxybenzoic acid: hydrazine 1, a hydrating agent (such as ascorbic acid), a coloring agent, a flavoring agent, and/or sweetness. Such as, sugar, saccharin or aspartame). The active ingredient can be suspended in vegetable oil (such as peanut oil, general 140628.doc -63-201002728 oil, sesame oil or coconut oil) or mineral oil (such as liquid paraffin drought *, Άδ weekly oily sweat). Oily suspension It may also contain a thickening agent, such as bee larvae, zebra gamma 7 , hard stone, or alcohol. A sweetener (such as the ones listed above) may be added. =: anti-emulsifier to preserve these compositions. Dispersible granules suitable for the preparation of aqueous suspensions by the addition of water - generally contain the active ingredient together with dispersing or wetting agents, suspending agents and antiseptic Suitable dispersing or wetting agents and suspending agents are described in the above two examples. Other excipients such as sweeteners, flavoring agents and tartans may also be present. The pharmaceutical composition of the present invention may also be in the form of water. In the form of an oil-in-water emulsion. The oil phase may be a vegetable oil such as olive oil or peanut oil, or an oil such as liquid, or any mixture of such materials. Suitable emulsifiers may be (for example, a wide gel: such as gum arabic or Astragalus gum), natural phospholipids , Soybean, Indian dish fat), derived from a partial or stuffed purpose g fatty acid and hexanoic anhydrides of material (e.g., sorbitan monooleate vinegar) and those partial condensation products of ethylene oxide Cool the hospital, Zhu

Such as polyoxyethylene sorbitan monooleic acid vinegar, may also contain sweeteners, flavoring agents and preservatives. H ▲ syrups and granules may be formulated with a sweetener such as glycerin, propylene glycol, sorbitol, aspartame or sucrose, and 1 may also contain a demulcent, preservative, flavoring and/or coloring agent. The pharmaceutical composition may also be in the form of a sterile injectable aqueous or oily suspension, which may be formulated according to one or more of the above-described suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be in the form of a non-toxic, injectable solution or suspension of a parenterally acceptable diluent or solvent, for example, a solution in 1,3-butanediol. The compositions for inhalation may be in the form of a conventional pressurized aerosol which is configured to dispense the active ingredient as a finely divided solid or liquid aerosol. Conventional aerosol propellants such as volatile fluoride fumes or fumes can be used, and the aerosol device can be conveniently configured to dispense an amount of active ingredient.

For additional information on formulations, please refer to Cehensive Medicinal Chemistry (c〇rwin Hanseh; Chairman of the Editorial Board), Pergamon Press 1990, Vol. 5, Chapter 25. The amount of active ingredient that will be combined with the multi-formulation agent to produce a single form will necessarily vary with the subject being treated and the particular route of administration. For example, formulations intended for oral administration to humans will generally contain, for example, from 0.5 to 2 g of active agent and may vary from about 5% to about 98% by weight of the total composition. Suitable and convenient amounts of excipients are compounded. The unit dosage form will generally contain from about 1 mg to about 5 mg of the active ingredient. For additional information on routes of administration and dosing protocols, the reader is referred to Co-* chemistry (corwin Hansch; Chairman of the Editorial Board), Pergam〇n Press 1990, Vol. 5, Chapter 25.3. The present invention can be used as a sole therapy, or in addition to the compounds of the present invention, in addition to the compounds of the present invention, or a variety of other substances and/or treatments. This combination therapy can be administered by a simultaneous, continuous, continuous or independent treatment of individual components, and when administered continuously or independently, the delay in the administration of the second component should not be paid, and the benefit of σ The effect is lost. Suitable species and substances may be selected from one or more of the following: 140628.doc -65 - 201002728 i) Other antibacterial agents, such as macrolides, such as erythromycin, azithromycin Or clarithromycin; quinolone, such as ciprofloxacin (cipr〇n〇xacin) or levofloxacin (lev〇fl〇Xacin); indoleamine, such as penicillin, such as amoxicillin or piperazine Piperacin; cephalosporin 'eg ceftriaxone or ceftazidime; carbapenem, such as meropenem or imipenem ( Imipenem), etc.; amino sugars such as gentamicin or tobramycin; or oxazolidinone; and/or ii) anti-infective agents, such as antifungal triazoles (for example) Or an amphotericin (and/or ill) biological protein therapeutic, such as an antibody, a cytokine, a bactericidal protein-enhancing protein (BPI) product; and/or iv) a liposome inhibitor. ^ Thus, in another aspect of the invention, there is provided a compound of formula (1), or a salt thereof which is pharmaceutically acceptable, and a chemotherapeutic agent selected from the group consisting of: Ο- or a plurality of other antibacterial agents; And/or u) - or a plurality of anti-infective agents; and / or u) biological protein treatments such as antibodies, cytokines, bactericidal/permeability increasing protein (BPI) products; and / or 1V) - or a variety of efflux pumps Inhibitor. In another embodiment, the invention relates to a method for treating infections such as human motility and sputum infection, which comprises administering to the animal an effective amount of formula (I) 140628.doc -66 - 201002728 and selected from the following a chemical compound of each substance or a pharmaceutically acceptable salt therapeutic agent thereof: 1) one or more other antibacterial agents; and/or ii) or a plurality of anti-infective agents; and/or U1) biological protein therapeutic agents such as antibodies , cytokine, bactericidal/permeability increasing protein (BPI) product; and/or iv) - or multiple efflux pump inhibitors.

As described above, the amount of the agent required for the therapeutic or prophylactic treatment of a particular condition will depend on the subject being treated, the route of administration, the severity of the condition being treated, and the combination of the compound of the present invention. Other chemotherapeutic agents vary. A daily dose in the range of (four) mg/kg is preferred. The daily dose will vary depending on the subject being treated, the particular route of administration, the severity of the condition being treated, and whether or not a combination of other chemical therapeutic agents are administered in combination with a compound of the present invention. Thus the 'optimal dose' can be determined by the practitioner treating any particular patient. As described above, one embodiment of the present invention is directed to the treatment or prevention of a disease caused by a bacterial infection, wherein the bacterium comprises GyrB ATPase or a topoisomerase-IV ATPase enzyme. "Treatment of an individual suffering from a disease caused by a bacterial infection" includes partial or substantial achievement of one or more of the following: reducing or improving the progression, severity and/or duration of the infection, curbing the spread of infection, and improving Or improve the clinical symptoms or indicators associated with infection (all tissues or serum components)' and prevent infection recurrence. As used herein, the term "preventing a bacterial infection" means reducing the risk of obtaining an infection' or reducing or inhibiting the recurrence of an infection. In a preferred embodiment 140628.doc-67.201002728, a compound of the invention is administered to a patient, preferably a human, as a prophylactic measure, followed by a surgical procedure to prevent infection. As used herein, the term "effective amount" means that the amount of a compound of the invention used to treat or prevent a bacterial infection is sufficient to prevent the onset of infection, reduce or improve the severity, duration or progression of the infection, prevent infection progression, and cause Attenuation of infection, prevention of recurrence, progression, onset or progression of symptoms associated with infection, or enhancement or amelioration of the prophylactic or therapeutic effect of another therapy. 0 In addition to use in therapeutic drugs, compounds of formula (1) and Its pharmaceutically acceptable salts are also suitable for development and standardization for the evaluation of inhibitors of DNA gyrase and/or topoisomerase iv in laboratory animals (such as cats, dogs, rabbits, monkeys, rats and small The pharmacological tools in the in vitro and in vivo test systems that act in mice are part of the search for new therapeutic agents. Among the other pharmaceutical compositions, processes, methods, uses, and pharmaceutical manufacturing features described above, alternatives and specific embodiments of the compounds of the invention described herein are also applicable. EXAMPLES The invention is illustrated by the following examples, but the invention is not limited to the following examples, wherein 'unless otherwise stated, (1) evaporation by rotary evaporation in a vacuum and removal of residue by filtration The solid is then subjected to a treatment procedure; () is generally operated at ambient temperature within the range of 1 8-26 ° C, and unless otherwise stated or unless otherwise familiar to those skilled in the art, Exclude air; 140628.doc -68- 201002728 (111) Unless otherwise stated, the column chromatography (by a flash procedure) was used to purify the compound and was performed on Merck Kieselgel bismuth (Art. 9385); Iv) the yield is given for illustrative purposes only and does not have to be the maximum available, the structure of the final product of the invention is generally confirmed by NMR & mass spectrometry; proton magnetic resonance spectroscopy is provided and unless otherwise stated It is typically measured in DMSO-d6 using a Bruker DRX-300 spectrometer operating at 300 MHz field strength. Low field chemical shift (δ scale) from tetradecyl decane as an internal standard reported in parts per million, and thus shows peak multiplicity: s, singlet; d, doublet; AB4dd, double and double Peak; shot, double triplet; dm, double multiplet; t, triplet; m, multiplet; 汾, broad peak; generally using a platform spectrometer operating with electrospray (provided by Micr〇mass) to obtain fast atom bombardment (FAB) mass spectrometry data, and if appropriate, collect cation or anion data, or use Agilent 1100 series [(:/)^8〇 equipped with Sedex 75ELSD operating in atmospheric pressure chemical ionization mode to obtain fast atom bombardment (FAB) mass spectrometry Data, and where appropriate, collect cation or anion data; mass spectrometry operates at 70 electron volts of electron energy in chemical ionization (CI) mode using direct exposure probes; the indicated ionization is caused by electron impact (EI), Fast atom bombardment (FAB) or electrospray (Esp) implementation, giving m/z values; in general, only ions indicating maternal mass are reported; (vi) standards required to purify each intermediate to subsequent stages and enough Finely characterized to confirm that the specified structure is correct; purity is assessed by high pressure liquid chromatography, thin layer chromatography or NMR, and is characterized by infrared spectroscopy (IR), mass spectrometry or NMR spectroscopy as appropriate 140628.doc -69- 201002728 (vii) The following abbreviations may be used: ACN is acetonitrile; CDC13 is deuterated gas; DBU is 1,8-diazabicyclo[5_4.0]H--7-ene; DCM Dioxane; DIEA is diisopropylethylamine; DMF is W-dimercaptoamine; DMSO is dimethyl sulfoxide; EDC is 1-ethyl-3-(3-didecylamino) Propyl) carbodiimide;

EtOAc was ethyl acetate;

EtOH is ethanol; HATU is N-[(didecylamino)-1Η,2,3-triazolo[4,5-b_]pyridin-1-ylfluorenylene]-N-fluorenyl hexafluorophosphate曱 ammonium N-oxide; HOBT is 1-hydroxybenzotriazole;

MeOH is decyl alcohol; MS is mass spectrum; RT or rt is room temperature; SM is the starting material; TFA is trifluoroacetic acid; TFAA is trifluoroacetic anhydride; THF is tetrahydrofuran; and (viii) temperature is provided in ° 〇. Example 1 1-Ethyl-3-(5'-(5-o-oxy-4,5-diar-ar-,3,4-oxadiazol-2-yl)-4-(pyridyl 140628.doc - 70- 201002728 pyridin-2-ylethynyl)_3,3,-pyridin-6-yl)urea

(1-(4-Bromo-5,-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-3,3'-bipyridine-6 -yl)_3_ethylurea (intermediate 1,62 mg, 0.15 mmol), 2-ethynyl η ratio bite (15.78 mg, 0.15 mmol), moth copper (1) (1.457 mg, 7.65 μιηοΐ), three A mixture of ethylamine (0.064 mL, 0.46 mmol) and dichlorobis(triphenylphosphine)palladium(11) (5.37 mg, 7.65 μιηοΐ) was suspended in acetonitrile (5 mL) and heated in microwave for 6 h. It was cooled to room temperature, filtered through EtOAc (EtOAc) (EtOAc)EtOAc. : 428 (MH+), C22H17N703. ^-NMR (DMSO-d6) δ: l.ll (t, 3H); 3.21 (q, 2H); 7.43 (t, 1H); 7.52 (d, 1H); t, 1H); 7.83 (t, 1H); 7.88 (s, 1H); 8.47 (s, 1H); 8.51 (s, 1H); 8.59 (d, 1H); 9.0 (s, 2H); 9.49 (s , 1H); 12.80 (br, 1H). Example 2 1-Ethyl-3-(4-ethylidyl-5'-(5-sideoxy-4,5-dihydro-1,3,4- Rabbit succinyl-2-ylpyridin-6-yl)urea 140628.doc -71- 201002728

1-Ethyl-3-(5'·(5_sideoxy-4,5-dihydro-indole, 3 4 oxadiazolyl-4_((trimethyldecyl)ethynyl)-3) , 3,-bipyridyl-6-yl)urea (Example 3, 84 mg '〇·20 mm〇1) was suspended in decyl alcohol (5 ml). Na〇H (2, 2'00 mmol) was added and The mixture was stirred at room temperature for 2 hr. An aqueous solution of HCl (2 N) was added until pH reached 65. DCM (10 ml) was added and the organic layer was separated and washed with brine and dried over EtOAc. The volume of mL was added. Hexane was added and the resulting precipitate was filtered and washed with DCM to afford the desired product (25 mg) MS (ESP) 351 (MH*), C17H14N603 !H-NMR (DMSO-d6): 1.10 ( t, 3H); 3.20 (m, 2H); 4.66 (s, 1H); 7.61 (m, 1H); 7.78 (s, 1H); 8.34 (m, 1H); 8.41 (s, 1H); 8.92 (d , 1H); 8.98 (d, 1H); 9.43 (s, 1H); 12.84 (br, 1H) ppm Example 3 1-hexyl-3-(5*-(5-side gas group-4,5--one Nitrogen-1,3,4-anthracene-2 -yl)·4·((trimethyldecyl)hexynyl)-3,3^bipyridin-6-yl)urea

140628.doc -72- 201002728 1-(4-Bromo-5'-(5-sided oxy-4,5-dihydro-1,3,4-oxadiazol-2-yl)-3,3 '-Bipyridyl-6-yl)-3-ethylurea (intermediate 1,400 mg, 0.99 mmol), ethyl bromide trimethylcarbazide (116 mg, 1 · 18 mmol), copper telluride (1) (18.80 mg, O.io mmol), Et3N (0.550 mL, 3.95 mmol) and Pd(PPh3)4 (57.1 mg, 0.05 mmol) were combined in anhydrous DMF (10 mL) and heated at 80 ° C for 4 hours . After cooling to room temperature, the crude sample was filtered through EtOAc (EtOAc) (EtOAc) elute MS (ESP) 423 (MH^) C20H22N6O3Si^-NMR (DMSO-d6): 0.12 (s, 9H); 1.10 (t, 3H); 3.20 (m, 2H); 7.57 (m, 1H); 7.72 (s , 1H); 8.41 (m, 1H); 8.45 (s, 1H); 8.92 (d, 1H); 8.99 (d, 1H); 9.41 (s, 1H); 12.86 (s, 1H) ppm Intermediate 1 1 -(4-bromo-5'-(5-oxo-oxy-4,5-dihydro-1,3,4-oxadiazole-2-yl)-3,3,-聨"ifc bite-6 ·Base)-3 -ethyl gland

Y will be (1 -(4-di-5'-(indenyl)_3,3'-linked η ratio -6-yl)-3-ethylurea (intermediate 2, 60 mg, 0.16 mmol), a mixture of 1,1,-carbonylbis(li/-imidazole) (34.4 mg, 0.21 mmol) and diisopropylethylamine (0.041 ml, 0-24 mmol) in 140628.doc •73-201002728 DMF (3 ml) It was heated at 5 Torr for 4 hours and then cooled to room temperature. The crude residue was concentrated under reduced pressure and purified by column chromatography (j. MS (ESP): 407 (MH+), C15Hl3BrN6 〇3. W-NMR (DMSO-d6) δ: 1.09 (t,3H); 3.19 (t , 2H); 7 48 (tm); 8. 〇 4 (s, 1H); 8.23 (t, 1H); 8.29 (slH); 88 〇 (d ^ 9.0 (d, 1H); 9.45 (s, 1H) ' Intermediate 2 1-(4-淡-5'-(耕叛基)-3,3,-联*比咬-6-yl)_3_ethyl gland

4 4'-Bromo-6'-(3-ethylureido)-3,3'-bipyridyl 5-carboxylic acid ethyl ester (intermediate 3, 1.32 g, 2.85 mmol) and hydrazine hydrate (1.416 〇1) After 53 mmol) was mixed in ethanol (20 ml), heated at 80 °C for 2 days, and then; The resulting residue was diluted with ethyl acetate. The resulting precipitate was collected by filtration and washed with ethyl acetate (920 mg). MS (ESP): 381 (MH+), C14H15BrN6 〇2^-NMR (DMSO-d6): 1.08 (t,3H); 3.17 (q,2H); 3·58 (br 2H); 7.43 (t, 1H) ; 8.05 (s, 1H); 8.27 (s, 2H); 8.85 (s 1H)· 9.03 (s, 1H); 9.43 (s, 1H); 11.15 (br, 1H). 140628.doc -74· 201002728 Intermediate 3 4,-Bromo-6,-(3-ethylureido)_3,3,_躜pyridin-5-carboxylic acid ethyl ester

1-(4-Bromo-5-iodopyridin-2-yl)-3-ethylurea (Intermediate 4, 1.33 g, 3.59 mmol), 5-(4,4,5,5-tetramethyl- 1,3,2-diboron taste_2-yl) in acid ethyl ester (1.049 g, 3.59 mmol), decyltriphenylphosphine | bar (0.415 g, 0.36 mmol) and K2CO3 (0.745 g, 5, 39 A mixture of mmol) was suspended in a mixture of DMF (10 mL) and water (1.000 mL). The suspension was degassed and purged with nitrogen and heated at 100 ° C for 1.5 h. The reaction mixture was cooled to room temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by hydrazine column chromatography gave the desired product (1.32 g). MS (ESP): 395 (MH, C16H17BrN403. 'H-NMR (CDC13): 1.29 (t, 3H); 1.45 (t, 3H); 3.45 (q, 2H); 4.47 (q, 2H); 7.30 ( Br, 1H); 8.12 (s, 1H); 8.38 (t, 1H); 8.84 (2s, 2xH); 9.29 (s, 1H). Intermediate 4 1-(4-bromo-5-iodopyridine-2_ Base)-3-ethylurea 140628.doc -75- 201002728

Treatment of 4-bromo-5-iodopyridin-2-amine (intermediate 5, 3.2 g, 10.71 mmol) in isocyanatoethane (2.52 mL '32.12 mmol) in dry air (15 mL) The solution was heated and the reaction mixture was heated to reflux for 24 h. The reaction mixture was cooled to room temperature and hexane was added. The desired product formed a precipitate which was collected by filtration (yield: 3.14 g). MS (ESP): 371 (MH,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, (s, 1H); 9.31 (s, 1H). Intermediate 5 4-bromo-5-mothidine-2-amine

Add 1-iodopyrrolidine-2,5-dione (6 5 溶液) to a solution of 4-bromopyridin-2-amine (2.5 g, 14.45 mmol) in DMF (6 mL) / EtOAc (20 mL) 28.90 mm〇l). The reaction mixture was stirred at 45 ° C for 2 days. The chloroform was removed under reduced pressure and the remaining solution was poured into water (15 mL) and extracted with Et.sub. The organic phase was concentrated under reduced pressure. Purification by column chromatography (EtOAc EtOAc) elute MS (ESP): 298 (1^11*), CsH4BrIN2. I40628.doc -76· 201002728 ^-NMR (DMSO-d6): 4.51 (br, 2H); 6.80 (s, 1H); 8.35 (s, 1H).

140628.doc -77-

Claims (1)

201002728 VII. Patent application scope: 1. A compound of formula (I): Or a pharmaceutically acceptable salt thereof, wherein: X is N, CH or CR4; L is Ci_6 alkyl, -ch=ch_(Ci 4 alkyl) or 丨* When L is -CH, #"Extended base) or _Csc_(Ci *Extended base), the double bond or the bond is a point of attachment to the ring A; R1 is selected from: Cw alkyl, c2_6 alkenyl , C2-6 alkynyl or c"cycloalkyl; wherein R1 may be substituted on the carbon by one or more R7, R is selected from hydrogen or c,-6 alkyl; wherein the Ci0 alkyl is visible The case is substituted with one or more groups independently selected from the group consisting of a dentate group, a cyano group, a hydroxy group, a nitro group and an amine group; or R1舆R2 together with the nitrogen to which it is attached form a heterocyclic group; wherein the heterocyclic group is visible Wherein the case is substituted by one or more R 8 ' on one or more carbon atoms and wherein if the heterocyclic group contains a =N_ or _s_ moiety, the nitrogen may optionally be substituted with a pendant oxy group and the sulphur may be optionally Substituted by one or two pendant oxy groups; and wherein if the heterocyclic group contains a _NH_ moiety, the nitrogen may optionally be substituted with a group selected from R9; R3 is hydrogen, Ck alkyl, (Ci 6 alkyl) 3矽 alkyl, c3_14 carbocyclyl or 14 0628.doc 201002728 Heterocyclyl, wherein optionally substituted at - or a plurality of carbon atoms - or a plurality of R, and wherein if the heterocyclic group contains a good or a moiety, the nitrogen may be as it is The fluorenyl group is substituted and the sulphur may be substituted by a pendant oxy group and wherein if the heterocyclic group contains a _ -- moiety, the hydrazine nitrogen may optionally be substituted with a group selected from R 11; Is independently selected from the group consisting of: halo-based, cyano, trans-amino, thiol, c", ^ & alkenyl, C2-6 alkynyl, Cl-6 Alkoxy, alkyl)amino, acryl) 2 amine and C1• thiol; wherein each occurrence of r4 independently depends on 5 conditions on one or more carbon atoms via one or more r] 2 is substituted; R is hydrazine or a heterocyclic group; wherein the heterocyclic group may be optionally substituted with -〇, =s or one or more r14 at - or a plurality of atoms; and wherein if the hetero-amino 3H or _s·部分', the nitrogen may be optionally substituted by a pendant oxy group and the sulphur may be optionally substituted with or with two pendant oxy groups; and wherein: the heterocyclic group contains a _NH_ moiety, then As the case may be, the group is substituted; t R6 is independently selected from the group consisting of the following groups: i group, nitro group, cyano group, hydroxyl group, amine group, sulfhydryl group, amine sulfonium group , Ci-6 alkyl, c2.6 alkenyl, c2.6 alkynyl, c,-6 alkoxy, WCw leu) amine, a(Ci 6 alkyl) 2 amine, C "alkyl 8仇_ , where & is 0, 1 or 2, #-(c"6 alkyl) sulfonyl sulfonyl u_(Ci 6 phenyl) 2 amine fluorenyl, Cl.6 alkyl carbylamine, C3 .14<cyclic and heterocyclic; wherein each occurrence of R6, independently, optionally substituted with one or more R16 on one or more carbon atoms; and wherein if the heterocyclic group contains = or _8_140628 .doc 201002728 part 'The nitrogen may be replaced by one or two pendant oxy groups as the case may be; part of the nitrogen may optionally be selected as 0 or 1; the pendant oxy group is substituted and the sulphur may be If the heterocyclic group contains _NH_ substituted from the group of Rl3; p is 0, 1, 2 or 3; the B ring is a C: 3_M carbocyclic group or a heterocyclic group; and the -NH- moiety thereof, the nitrogen may optionally be selected from the group if the heterocyclic group contains =N_ or a part , a pendant oxy group substituted and the sulfur may be substituted; if the heterocyclic group contains a group substituted with R.sup.5; and the nitrogen may optionally be taken by one or two pendant oxy groups, R R 8 ' R , R and 16 is a substituent on carbon, which is independently selected from the group consisting of, succinyl, cyano, thiol, amine, ruthenium, amine, thiol, acesulfame, thiol, uryl, and thiol. , C2_6 alkyne &, Cl_6 alkoxy, c "alkyl fluorenyl, C] - alkyl fluorenyl s, 'mc, .6 alkyl) amine m m base) 2 amine, Ci (tetra) yl n-alkyl Amine-based, #((:1_6 alkyl) 2 amine-based, Cl-6 alkyl S(〇)a-, where 4〇, U2, Ci6Mg, c-6-6 alkoxyamine a group, i (Cl. 6 alkyl) sulfonyl m) 2 amine fluorenyl, cyclylamino, _l2_C3_4 or -L-heterocyclic; wherein R7, R8, Rl0, r12, Rl4 and Ri6, independently of each other, may be substituted on one or more carbons by one or more R19; and wherein Wherein the heterocyclic group contains a moiety, the nitrogen may optionally be substituted with a group selected from r2i, and wherein: the heterocyclic group contains a =N_ or _s_ moiety, the nitrogen may optionally be substituted with a pendant oxy group And the sulfur may be substituted by two side oxy groups of one or R 140628.doc 201002728; L is a direct bond, _〇_, _N ()~ '-C(〇)- s -N(R18)C(O )-, -C(0)N(R18)-, _Sr〇, ^ ..〇18>. AV, -S〇2N(R18)- or _N(R'S〇2_; where R is born independently of Is d9 nn β is 虱 or Cn4 alkyl and p is 〇_2 ; R9' R13^ r.7 The singular K-matrix appears independently from Ci_6 alkyl, c3.6 ring, Γ ^ _ Cl -6 alkyl fluorenyl, Cl 6 alkyl sulfonyl, C! _ 6 alkoxy group, amine methyl broth T base, ^ v _ (Ci 6 alkyl) amine carbaryl, 丨 6 alkyl) amine Sulfhydryl, | allyl methyl, stupid methoxycarbonyl, benzhydryl and phenylsulfonyl; wherein R9, R", r 3, R15, R" and r2. independently of each other on carbon Substituted by one or more of r23; and each occurrence of R19 and R23 is independently selected from halo, nitro, cyano, thio, trifluoromethoxy, tri Fluoromethyl, amine, ruthenium, amine methyl sulfhydryl, decyl, sulfonyl, decyl, ethyl, methoxy, ethoxy, ethoxylated, ethoxylated, methylamino, Ethylamino, dimethylamino, diethylamino, ΛΓ-methyl- oxime ethylamino, etidinyl, methylamine, fluorenyl, decylamine Aminomethylmercapto, diethylaminoindenyl, methyl-iV-ethylaminecarbamyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, A Sulfonyl, ethylsulfonyl, hydrazine carbonyl, ethoxycarbonyl, methylamine sulfonyl, ethylamine sulfonyl, #, dimethyl sulfonyl, diethylamine Base or iV-mercapto-ethylamine sulfonyl. 2. 3. 4. The compound of claim 1 wherein X is CH. The compound of claim 1, wherein X is N. A compound of claim 1, 2 or 3 wherein l is -C^CHCmalkylene 140628.doc 201002728 base). 5. A compound of claim 1, 2 or 3 wherein l is). Alkane 6. A compound of claim 2 or 3 in which the base is extended. The compound according to any one of the preceding claims, wherein the B ring is 5 or a aryl group, wherein if the heteroaryl group contains a moiety, the nitrogen may be substituted with a group selected from R15; Wherein the heteroaryl group contains two moieties, the nitrogen optionally being substituted with one pendant oxy group and the condition being substituted with one or two pendant oxy groups. Month 8. The compound of any of the following items, wherein the ring B is pyridinium: a pyridyl group, a sulfhydryl group or a silk, in which a bite base. Each of the azine group, the bismuth or the oxime group may be independently substituted by a pendant oxy group, and the ss group of the thiazolyl group is substituted. Knife J wishing a barrier through one or two side oxygen 9. As requested in items 1 to 6 _ j苜 夕 儿 personnel, in which the anthracene ring is a bicyclic heterocyclic ring, "the middle right of the heterocyclic group contains _ΝΗ. d15 w ° 77, the nitrogen may be optionally substituted by a group; and wherein if the heterocyclic group contains =Ν_ or _s_ moiety II' (tetra), the nitrogen may be optionally substituted by a pendant oxy group The sulfur may be optionally substituted with one or two pendant oxy groups. 10. The compound of claim 9 wherein Α Γ 1 ^ is quinoxalinyl or 5,6-dihydroanthracene, 3]thiazolo[4,5 _岣哒.„ 奈奈,7—啊' where 5,6-dihydro[1,3]thiazole is opened [4,5-blade 哒嗓4,7_二纟—鲖之ΝΗ·ΝΗ- Independently, depending on the situation, - is replaced by a group of R. Chopin', and, 10,6-dihydro[1,3]thiazole [4,5-staprazine_4 7 _ , - ketone each = Ν - can be independently substituted by a pendant oxy group according to 140628.doc 201002728; and wherein _ dansin 5,6- 虱[1,3]thiazolo[4,5 The _s_ moiety of _闳4,7-dione may be optionally substituted with one or two (tetra)oxy groups. 11. 12. 13. 14. 16. 16. 17. 18. 19. The compound of any of the preceding claims, wherein r, ci- is a group. A compound of claim 11, wherein R1 is ethyl. A compound according to any one of the preceding claims, wherein r2 is a gas. Item: Any of the compounds 'where R3 is 5 or 嶋----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Where the aryl group contains a =N- or _s- moiety, the nitrogen may optionally be substituted with one pendant oxy group and the sulphur may be optionally substituted with one or two pendant oxy groups; and wherein if the heteroaryl group contains a moiety thereof, The nitrogen may then be substituted with a group selected from Rn. A compound of claim 4, wherein r3 is pyridyl. A compound according to any one of items 1 to 13, wherein R, hydrogen. A compound according to any one of claims 1 to 13 wherein R3 is a trimethylsulfonyl group. For example, any of the If/(I- yV AL, , 5 η " 贞 compounds" wherein R 5 is a five-membered aromatic cloche, wherein the heterocyclic group may be in the case of - or a plurality of carbon atoms... One or more Ri4 substitutions' and wherein if the heterocyclic group is contained, the mouse may be optionally substituted with one pendant oxy group and the sulfur may be substituted with one or two pendant oxy groups; If the heterocyclic group contains a _nh_ moiety, the nitrogen may be optionally substituted with a group selected from the group consisting of Hanmen. The compound of claim 18, wherein 5 is selected from the group consisting of azozolyl, anthracene, 3 , 4 · thiadiazolyl, 1/7-tetrazolyl, 140628.doc 201002728 1,2,4-oxadiazolyl, 1 pyrazolyl, 3β-1,2,3,5-oxothiazepine Azyl, 1#-imidazolyl, morpholinyl, 4,5-dihydro-oxazolyl and 1/-1,2,4-triazolyl, wherein the 1,3,4 oxadiazole Base, l,3,4-thiadiazolyl, li/-tetrazolyl, 1,2,4-oxadiazolyl, 1/--pyrazolyl, 377-1,2,3,5- Thiadiazolyl, lif-imidazolyl, morpholinyl, 4,5-dihydro-oxazolyl and 1/ί- 1,2,4-triazolyl may optionally be on one or more carbon atoms a plurality of R14 substitutions; and wherein 1,3,4-oxadiazolyl, 1,3,4-·», succinyl, succinyl, 1-tetrazolyl, 1,2,4-oxadiazolyl, Pyrazolyl, 3//-1,2,3,5-oxathiadiazolyl, lif-imidazolyl, 4,5-dihydro-oxazolyl and 1//-1,2,4-triazole The base = N- moiety may be optionally substituted with a pendant oxy group, and 丨, 3,4 thiadiazolyl or the _s- moiety of the 3//-1,2,3,5-oxathiadiazolyl group Substituted by one or two pendant oxy groups; and wherein the 1 //-tetrasyl group, 1 //- oxime. Sit, 3//-1, 2,3,5-oxathiadiazolyl, 1//_Imidazolyl, morpholinyl or the ΝΗ· moiety of the 1//1 1,2,4-triazolyl group may be optionally substituted with a group selected from r丨7. 20. A compound of 19, wherein rm is selected from the group consisting of Ci 4 alkyl or a trans group. 21. The compound of claim 18, 19 or 2, wherein R17 is Cm alkyl. 22. The compound of claim 18, The compound of any one of the preceding claims, wherein m is oxime, wherein p is a compound of any one of the preceding claims, wherein p is 〇 25. As just stated A compound of any one of the preceding claims, wherein p is 1. 26. A pharmaceutical composition comprising the compound of any of claims i to 25, 140628.doc 201002728, or a pharmaceutically acceptable salt thereof And pharmaceutically acceptable excipients or carriers. 27. A method of inhibiting bacterial dna gyrase and/or bacterial topoisomerase IV in a warm-blooded animal in need of treatment, comprising administering to the animal an effective amount of a compound of any one of claims 丨 to 25 , or a pharmaceutically acceptable salt thereof. 28. A method of producing an antibacterial effect in a warm-blooded animal in need of treatment, comprising administering to the animal an effective amount of a compound according to any one of claims 1 to 25 or a pharmaceutically acceptable compound thereof salt. 29. A method of treating a bacterial infection in a warm-blooded animal in need thereof, comprising administering to the animal an effective amount of the compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof. The method of claim 2, wherein the bacterial infection is selected from the group consisting of: community-type pneumonia, hospital-type infection pneumonia, skin and skin structure infection, acute exacerbation of chronic bronchitis, acute Sinusitis, acute otitis media, catheter-related sepsis, febrile neutropenia, osteomyelitis, endocarditis, urinary tract infections, and infections caused by drug-resistant bacteria, such as anti-penicillin Penicillin-resistant Arepiococcws pnewmomae, methicillin-resistant Staphylococcus aureus (methicillin-resistant epWerwWh) and vancomycin-resistant gut The method of any one of claims 27 to 30, wherein the warm-blooded animal is a human. 32. A request as claimed in any one of claims 1 to 25; Use of a compound or a pharmaceutically acceptable salt thereof for the manufacture of an antibacterial agent in a warm-blooded animal Use of a compound according to any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, for the manufacture of a bacterial DNA gyrase for use in inhibiting a warm-blooded animal and/or The use of a compound of any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, for the manufacture of a bacterium for treating a warm-blooded animal Infectious drug. 35. The use of claim 34, wherein the bacterial infection is selected from the group consisting of: community-type pneumonia, hospital-type infection pneumonia, skin and skin structure infections, acute exacerbation of chronic bronchitis, Acute sinusitis, acute otitis media, catheter-related sepsis, febrile neutropenia, medullary inflammatory disease, endocarditis, urinary tract infection, anti-penicillin pneumococci, methicillin-resistant gold Staphylococcus aureus, Staphylococcus epidermidis against methicillin and enterococci against vancomycin 36. The use of any of items 32 to 35, wherein the warm-blooded animal is a human. Such as A compound of the formula (25), or a pharmaceutically acceptable salt thereof, for use in the production of an antibacterial effect in a warm-blooded animal. 3 8. ^ β月求求到25中任— a compound of the formula, or a pharmaceutically acceptable salt thereof, for use in inhibiting the bacterium of the warm-blooded animal, the turpentine rotase and/or 140628.doc 201002728 topoisomerase ιν. 3 9. As claimed in claim 1 A compound according to any one of 25, or a pharmaceutically acceptable salt thereof for use in the treatment of a bacterial infection in a warm-blooded animal. The compound of any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, for use in the treatment of community-type pneumonia, hospital-type infection pneumonia, skin and skin structure infections, chronic bronchitis Acute exacerbation, acute sinusitis, acute otitis media, catheter-related sepsis, febrile neutropenia, osteomyelitis, endocarditis, urinary tract infection, Streptococcus pneumoniae resistant to penicillin, anti-dioxanthromycin Staphylococcus aureus, Staphylococcus epidermidis against phthalicillin or Enterococci against vancomycin. 140628.doc 10- 201002728 IV. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 5. If there is a chemical formula in this case, please reveal the best display invention. Characteristic chemical formula: 140628.doc